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Recessive Mutation (recessive + mutation)

Distribution by Scientific Domains

Life Sciences	83%
Medical Sciences	16%

Selected Abstracts

Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion,

HUMAN MUTATION, Issue 7 2010
Nigel F. Clarke
Abstract The main histological abnormality in congenital fiber type disproportion (CFTD) is hypotrophy of type 1 (slow twitch) fibers compared to type 2 (fast twitch) fibers. To investigate whether mutations in RYR1 are a cause of CFTD we sequenced RYR1 in seven CFTD families in whom the other known causes of CFTD had been excluded. We identified compound heterozygous changes in the RYR1 gene in four families (five patients), consistent with autosomal recessive inheritance. Three out of five patients had ophthalmoplegia, which may be the most specific clinical indication of mutations in RYR1. Type 1 fibers were at least 50% smaller, on average, than type 2 fibers in all biopsies. Recessive mutations in RYR1are a relatively common causeof CFTD and can be associated with extreme fiber size disproportion. © 2010 Wiley-Liss, Inc. [source]

Mutation spectrum of MYO7A and evaluation of a novel nonsyndromic deafness DFNB2 allele with residual function,,

HUMAN MUTATION, Issue 4 2008
Saima Riazuddin
Abstract Recessive mutations of MYO7A, encoding unconventional myosin VIIA, can cause either a deaf-blindness syndrome (type 1 Usher syndrome; USH1B) or nonsyndromic deafness (DFNB2). In our study, deafness segregating as a recessive trait in 24 consanguineous families showed linkage to markers for the DFNB2/USH1B locus on chromosome 11q13.5. A total of 23 of these families segregate USH1 due to 17 homozygous mutant MYO7A alleles, of which 14 are novel. One family segregated nonsyndromic hearing loss DFNB2 due to a novel three-nucleotide deletion in an exon of MYO7A (p.E1716del) encoding a region of the tail domain. We hypothesized that DFNB2 alleles of MYO7A have residual myosin VIIA. To address this question we investigated the effects of several mutant alleles by making green fluorescent protein (GFP) tagged cDNA expression constructs containing engineered mutations of mouse Myo7a at codons equivalent to pathogenic USH1B and DFNB2 alleles of human MYO7A. We show that in transfected mouse hair cells an USH1B mutant GFP-myosin VIIa does not localize properly to inner ear hair cell stereocilia. However, a GFP-myosin VIIa protein engineered to have an equivalent DFNB2 mutation to p.E1716del localizes correctly in transfected mouse hair cells. This finding is consistent with the hypothesis that p.E1716del causes a less severe phenotype (DFNB2) than the USH1B -associated alleles because the resulting protein retains some degree of normal function. Hum Mutat 29(4), 502,511, 2008. Published 2008 Wiley-Liss, Inc. [source]

Lesions in the mRNA cap-binding gene ABA HYPERSENSITIVE 1 suppress FRIGIDA -mediated delayed flowering in Arabidopsis

THE PLANT JOURNAL, Issue 1 2004
Isabel C. Bezerra
Summary Recessive mutations that suppress the late-flowering phenotype conferred by FRIGIDA (FRI) and FLOWERING LOCUS C (FLC) and which also result in serrated leaf morphology were identified in T-DNA and fast-neutron mutant populations. Molecular analysis showed that the mutations are caused by lesions in the gene encoding the large subunit of the nuclear mRNA cap-binding protein, ABH1 (ABA hypersensitive1). The suppression of late flowering is caused by the inability of FRI to increase FLC mRNA levels in the abh1 mutant background. The serrated leaf morphology of abh1 is similar to the serrate (se) mutant and, like abh1, se is also a suppressor of FRI -mediated late flowering although it is a weaker suppressor than abh1. Unlike se, in abh1 the rate of leaf production and the number of juvenile leaves are not altered. The abh1 lesion affects several developmental processes, perhaps because the processing of certain mRNAs in these pathways is more sensitive to loss of cap-binding activity than the majority of cellular mRNAs. [source]

Alsin/Rac1 signaling controls survival and growth of spinal motoneurons

ANNALS OF NEUROLOGY, Issue 1 2006
Arnaud Jacquier MSc
Objective Recessive mutations in alsin, a guanine-nucleotide exchange factor for the GTPases Rab5 and Rac1, cause juvenile amyotrophic lateral sclerosis (ALS2) and related motoneuron disorders. Alsin function in motoneurons remained unclear because alsin knock-out mice do not develop overt signs of motoneuron degeneration. Methods To generate an alsin loss-of-function model in an ALS-relevant cell type, we developed a new small interfering RNA electroporation technique that allows efficient knock down of alsin in embryonic rat spinal motoneurons. Results After small interfering RNA,mediated alsin knockdown, cultured motoneurons displayed a reduced apparent size of EEA1-labeled early endosomes and an increased intracellular accumulation of transferrin and L1CAM. Alsin knockdown induced cell death in 32 to 48% of motoneurons and significantly inhibited axon growth in the surviving neurons. Both cellular phenotypes were mimicked by expression of a dominant-negative Rac1 mutant and were completely blocked by expression of a constitutively active Rac1 mutant. Expression of dominant-negative or constitutively active forms of Rab5 had no such effects. Interpretation Our data demonstrate that alsin controls the growth and survival of motoneurons in a Rac1-dependant manner. The strategy reported here illustrates how small interfering RNA electroporation can be used to generate cellular models of neurodegenerative disease involving a loss-of-function mechanism. Ann Neurol 2006;60:105,117 [source]

NaV1.6a is required for normal activation of motor circuits normally excited by tactile stimulation

DEVELOPMENTAL NEUROBIOLOGY, Issue 7 2010
Sean E. Low
Abstract A screen for zebrafish motor mutants identified two noncomplementing alleles of a recessive mutation that were named non-active (navmi89 and navmi130). nav embryos displayed diminished spontaneous and touch-evoked escape behaviors during the first 3 days of development. Genetic mapping identified the gene encoding NaV1.6a (scn8aa) as a potential candidate for nav. Subsequent cloning of scn8aa from the two alleles of nav uncovered two missense mutations in NaV1.6a that eliminated channel activity when assayed heterologously. Furthermore, the injection of RNA encoding wild-type scn8aa rescued the nav mutant phenotype indicating that scn8aa was the causative gene of nav. In-vivo electrophysiological analysis of the touch-evoked escape circuit indicated that voltage-dependent inward current was decreased in mechanosensory neurons in mutants, but they were able to fire action potentials. Furthermore, tactile stimulation of mutants activated some neurons downstream of mechanosensory neurons but failed to activate the swim locomotor circuit in accord with the behavioral response of initial escape contractions but no swimming. Thus, mutant mechanosensory neurons appeared to respond to tactile stimulation but failed to initiate swimming. Interestingly fictive swimming could be initiated pharmacologically suggesting that a swim circuit was present in mutants. These results suggested that NaV1.6a was required for touch-induced activation of the swim locomotor network. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70:508,522, 2010 [source]

Deficits in the mid-brain raphe nuclei and striatum of the AS/AGU rat, a protein kinase C-, mutant

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2005
M. Al-Fayez
Abstract The AS/AGU rat carries a recessive mutation (agu) in the gene coding for the gamma isoform of protein kinase C. The rat is characterized by disordered locomotion and progressive dysfunction of the nigrostriatal dopaminergic (DA) system. This dysfunction begins with a failure to release DA within the striatum and culminates in cell loss within the substantia nigra pars compacta. The present study examines another midbrain aminergic system with input to the basal ganglia, the serotonergic (5-HT) raphe,striatal system originating in the dorsal raphe nucleus. By 3 months after birth, there is a very substantial reduction in the extracellular levels of 5-HT in the dorsal caudate-putamen of the mutants compared with controls (c. 70%). This is accompanied by a proportional increase in the levels of the 5-HT metabolite 5-hydroxyindole acetic acid (5-HIAA). At a later age, there are reductions in whole tissue 5-HT (and increases in 5-HIAA) in both the striatum and the region containing the dorsal raphe nucleus, as well as numbers of 5-HT-immunoreactive cells in the dorsal raphe nucleus. The median raphe appears to be unaffected. The results are seen in terms of an initial dysfunction in transmitter release leading to cell death, perhaps through the formation of free radicals or neurotoxins. [source]

D90A- SOD1 mediated amyotrophic lateral sclerosis: A single founder for all cases with evidence for a Cis -acting disease modifier in the recessive haplotype,,

HUMAN MUTATION, Issue 6 2002
Matthew J. Parton
Abstract More than 100 different heterozygous mutations in copper/zinc superoxide dismutase (SOD1) have been found in patients with amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease. Uniquely, D90A- SOD1 has been identified in recessive, dominant and apparently sporadic pedigrees. The phenotype of homozygotes is stereotyped with an extended survival, whereas that of affected heterozygotes varies. The frequency of D90A- SOD1 is 50 times higher in Scandinavia (2.5%) than elsewhere, though ALS prevalence is not raised there. Our earlier study indicated separate founders for recessive and dominant/sporadic ALS and we proposed a disease-modifying factor linked to the recessive mutation. Here we have doubled our sample set and employed novel markers to characterise the mutation's origin and localise any modifying factor. Linkage disequilibrium analysis indicates that D90A homozygotes and heterozygotes share a rare haplotype and are all descended from a single ancient founder (alpha 0.974) c.895 generations ago. Homozygotes arose subsequently only c.63 generations ago (alpha 0.878). Recombination has reduced the region shared by recessive kindreds to 97-265 kb around SOD1, excluding all neighbouring genes. We propose that a cis -acting regulatory polymorphism has arisen close to D90A- SOD1 in the recessive founder, which decreases ALS susceptibility in heterozygotes and slows disease progression. © 2002 Wiley-Liss, Inc. [source]

Uniparental disomy and human disease: An overview,

AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 3 2010
Kazuki Yamazawa
Abstract Uniparental disomy (UPD) refers to the situation in which both homologues of a chromosomal region/segment have originated from only one parent. This can involve the entire chromosome or only a small segment. As a consequence of UPD, or uniparental duplication/deficiency of part of a chromosome, there are two types of developmental risk: aberrant dosage of genes regulated by genomic imprinting and homozygosity of a recessive mutation. UPD models generated by reciprocal and Robertsonian translocation heterozygote intercrosses have been a powerful tool to investigate genomic imprinting in mice, whereas novel UPD patients such as those with cystic fibrosis and Prader,Willi syndrome, triggered the clarification of recessive diseases and genomic imprinting disorders in human. Newly developed genomic technologies as well as conventional microsatellite marker methods have been contributing to the functional and mechanistic investigation of UPD, leading to not only the acquisition of clinically valuable information, but also the further clarification of diverse genetic processes and disease pathogenesis. © 2010 Wiley-Liss, Inc. [source]

Maize mutants affected at distinct stages of the arbuscular mycorrhizal symbiosis

THE PLANT JOURNAL, Issue 2 2006
Uta Paszkowski
Summary Maize mutants affected in the symbiotic interaction with the arbuscular mycorrhizal fungus Glomus mosseae have been found by a visual, macroscopic screen in a Mutator -tagged population of maize. Seven mutants have been identified, falling into three phenotypic classes. For each class one mutant has been characterized in more detail. The nope1 (noperception 1) mutant does not support appressoria formation of G. mosseae, suggesting the absence of a plant-encoded function necessary for early recognition prior to contact. The phenotype segregated as a monogenic recessive trait, indicating that a mutation in a single locus abolished compatibility of maize to G. mosseae. On a second mutant termed taci1 (taciturn 1), appressoria form at reduced frequency but their morphology is normal and leads to penetration of the rhizodermis. However, intraradically, the majority of hyphae are septate, resulting in terminated fungal spreading. This phenotype suggests that the mutation of taci1 has an effect on recognition and on cortex invasion. Segregation analysis indicates taci1 to carry a recessive mutation. In contrast, wild-type fungal morphology has been recorded in the Pram1 (Precocious arbuscular mycorrhiza 1) mutant, which displays enhanced and earlier fungal invasion. This trait segregates in a dominant fashion indicative of a gain-of-function mutation affecting the plant's control over restricting fungal colonization. [source]

Large-scale screening of Arabidopsis circadian clock mutants by a high-throughput real-time bioluminescence monitoring system

THE PLANT JOURNAL, Issue 1 2004
Kiyoshi Onai
Summary Using a high-throughput real-time bioluminescence monitoring system, we screened large numbers of Arabidopsis thaliana mutants for extensively altered circadian rhythms. We constructed reporter genes by fusing a promoter of an Arabidopsis flowering-time gene , either GIGANTEA (GI) or FLOWERING LOCUS T (FT) , to a modified firefly luciferase gene (LUC+), and we transferred the fusion gene (PGI::LUC+ or PFT::LUC+) into the Arabidopsis genome. After mutagenesis with ethyl methanesulfonate, 50 000 M2 seedlings carrying the PGI::LUC+ and 50 000 carrying PFT::LUC+ were screened their bioluminescence rhythms. We isolated six arrhythmic (AR) mutants and 29 other mutants that showed more than 3 h difference in the period length or phase of rhythms compared with the wild-type strains. The shortest period length was 16 h, the longest 27 h. Five of the six AR mutants carrying PGI::LUC+ showed arrhythmia in bioluminescence rhythms in both constant light and constant dark. These five AR mutants also showed arrhythmia in leaf movement rhythms in constant light. Genetic analysis revealed that each of the five AR mutants carried a recessive mutation in a nuclear gene and the mutations belonged to three complementation groups, and at least one of which was mapped on a novel locus. Our results suggest that the three loci identified here may contain central clock or clock-related genes, at least one of which may be a novel. [source]

A delayed leaf senescence mutant is defective in arginyl-tRNA:protein arginyltransferase, a component of the N-end rule pathway in Arabidopsis

THE PLANT JOURNAL, Issue 1 2002
Satoko Yoshida
Summary We have isolated a delayed-leaf-senescence mutant, designated dls1, from an Arabidopsis T-DNA line. Leaf senescence progresses more slowly in the dls1 mutant than in the wild-type plant in both age-dependent and dark-induced senescence. Genetic analysis revealed that the dls1 is a monogenic recessive mutation that cosegregated with the T-DNA insertion. Isolation of DNA flanking the T-DNA revealed that the T-DNA was inserted into the fourth intron of the AtATE1 gene, which encodes arginyl-tRNA:protein arginyltransferase (EC. 2.3.2.8, R-transferase), a component of the N-end rule proteolytic pathway in yeast and mammals that transfers arginine to the N-terminus of proteins with N-terminal glutamyl or aspartyl residues. AtATE1 transcripts were not detectable in the dls1 mutant by RT-PCR analysis. Introduction of a wild-type AtATE1 gene into the dls1 mutant complemented the dls1 phenotype. We also showed using a transient expression assay system, that the dls1 mutation results in a decreased degradation of proteins with Asp or Glu at their N-termini, and that the introduction of the wild-type AtATE1 gene reverses this deficiency. These results suggest that the normal progression of leaf senescence requires R-transferase activity, and that proteolysis by the N-end rule pathway has an important physiological function in the progress of leaf senescence in plants. [source]

Mutation in the melanocortin 1 receptor is associated with amber colour in the Norwegian Forest Cat

ANIMAL GENETICS, Issue 4 2009
M. Peterschmitt
Summary Amber (previously called X-Colour) is a yellow recessive coat colour observed in the Norwegian Forest Cat (NFC) population and apparently absent in other cat breeds. Until now, there has never been any scientific evidence of yellow recessive mutation (e) reported in the extension gene in Felidae. We sequenced the complete coding sequence region for the melanocortin 1 receptor in 12 amber, three carriers, two wild-type NFCs, one wild-type European Shorthair and two ,golden' Siberian cats and identified two single nucleotide polymorphisms (SNPs): a non-synonymous (FM180571: c.250G>A) and a synonymous (FM180571: c.840T>C) mutation. The c.250G>A SNP, further genotyped on 56 cats using PCR-RFLP, is associated with amber colour and only present in the amber cat lineages. It replaced an aspartic acid with a neutral polar asparagine in the second transmembrane helix (p.Asp84Asn), a position where e mutations have already been described. Three-dimensional models were built and showed electrostatic potential modification in the mutant receptor. With these results and together with those in the scientific literature, we can conclude that amber colour in NFCs is caused by a single MC1R allele called e, which has never been documented. [source]

A novel recessive Nefl mutation causes a severe, early-onset axonal neuropathy,

ANNALS OF NEUROLOGY, Issue 6 2009
Sabrina W. Yum MD
Objective To report the first cases of a homozygous recessive mutation in NEFL, the gene that encodes the light subunit of neurofilaments. Methods Clinical and electrophysiologic data were evaluated, and a sural nerve biopsy from one affected child was examined by immunohistochemistry and electron microscopy. The ability of the mutant protein to form filaments was characterized in an established cell culture system. Results Four of five siblings developed of a severe, progressive neuropathy beginning in early childhood. Serial nerve conduction studies showed progressively reduced amplitudes with age and pronounced slowing at all ages. Visual-evoked responses were slowed in three children, indicating that central nervous system axons were subclinically involved. All four affected children were homozygous for a nonsense mutation at glutamate 210 (E210X) in the NEFL gene; both parents were heterozygous carriers. A sural nerve biopsy from an affected patient showed markedly reduced numbers of myelinated axons; the remaining myelinated axons were small and lacked intermediate filaments. The E210X mutant protein did not form an intermediate filament network and did not interfere with the filament formation by wild-type human light subunit of neurofilaments in SW-13 vim, cells. Interpretation This is the first demonstration of a recessive NEFL mutation, which appears to cause a simple loss of function, resulting in a severe, early-onset axonal neuropathy with unique features. These results confirm that neurofilaments are the main determinant of axonal caliber and conduction velocity, and demonstrate for the first time that neurofilaments are required for the maintenance of myelinated peripheral nervous system axons. Ann Neurol 2009;66:759,770 [source]

Hair interior defect in AKR/J mice

CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 4 2009
K. A. Giehl
Summary Background., All AKR/J mice have a subtle defect that involves malformation of the central portion of hair fibres that is best visualized under white and polarized light microscopy. Aims., This study sought to characterize the clinical and ultrastructural features of the hair interior defect (HID) phenotype and to determine the chromosomal localization of the hid mutant gene locus. Methods., White and polarized light microscopy combined with scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to characterize the HID phenotype. Complementation testing and gene-linkage studies were performed to map the locus. Results., Using SEM, the hair-fibre structure on the surface was found to be similar to hairs obtained from normal BALB/cByJ+/+and C57BL/6 J+/+mice. There were also no differences in sulphur content. TEM revealed degenerative changes in the medulla similar to that seen by light microscopy. This autosomal recessive mutation is called HID (locus symbol: hid). We mapped the hid locus to the distal end of mouse chromosome 1. No genes reported to cause skin or hair abnormalities are known to be within this interval except for the lamin B receptor (Lbr), which had been excluded previously as the cause of the hid phenotype in AKR/J mice. Conclusion., A potentially novel gene or known gene with a novel phenotype resides within this interval, which may shed light on human diseases with defects in the inner structure of the hair fibre. [source]

Functional characterization of compound heterozygosity for GlyR,1 mutations in the startle disease hyperekplexia

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2002
Ruth Rea
Abstract The human disease hyperekplexia is characterized by excessive startle reactions to auditory and cutaneous stimuli. In its familial form, hyperekplexia has been associated with both dominant and recessive mutations of the GLRA1 gene encoding the glycine receptor ,1 subunit (GlyR,1), which mediates inhibitory transmission in the spinal cord and brainstem. Here we have examined the functional consequences of two amino acid substitutions found in a compound heterozygous family, R252H and R392H, to investigate the mechanisms determining this inheritance pattern. When expressed in Xenopus laevis oocytes, both mutations were non-functional. Neither mutant affected the electrophysiological properties of wild type GlyR,1 when co-expressed. We introduced a green fluorescent protein tag to mutant subunits and found that both mutant proteins were detectable. Evidence that subcellular localization differed from wild type was significant for one of the mutants. Thus, an effective loss of functional GlyR,1-mediated current underlies hyperekplexia in this family, whereas a partial loss is asymptomatic. [source]

HOW ARE DELETERIOUS MUTATIONS PURGED?

EVOLUTION, Issue 12 2003
DRIFT VERSUS NONRANDOM MATING
Abstract Accumulation of deleterious mutations has important consequences for the evolution of mating systems and the persistence of small populations. It is well established that consanguineous mating can purge a part of the mutation load and that lethal mutations can also be purged in small populations. However, the efficiency of purging in natural populations, due to either consanguineous mating or to reduced population size, has been questioned. Consequences of consanguineous mating systems and small population size are often equated under "inbreeding" because both increase homozygosity, and selection is though to be more efficient against homozygous deleterious alleles. I show that two processes of purging that I call "purging by drift" and "purging by nonrandom mating" have to be distinguished. Conditions under which the two ways of purging are effective are derived. Nonrandom mating can purge deleterious mutations regardless of their dominance level, whereas only highly recessive mutations can be purged by drift. Both types of purging are limited by population size, and sharp thresholds separate domains where purging is either effective or not. The limitations derived here on the efficiency of purging are compatible with some experimental studies. Implications of these results for conservation and evolution of mating systems are discussed. [source]

Molecular spectrum of SLC22A5 (OCTN2) gene mutations detected in 143 subjects evaluated for systemic carnitine deficiency,

HUMAN MUTATION, Issue 8 2010
Fang-Yuan Li
Abstract Systemic primary carnitine deficiency (CDSP) is caused by recessive mutations in the SLC22A5 (OCTN2) gene encoding the plasmalemmal carnitine transporter and characterized by hypoketotic hypoglycemia, and skeletal and cardiac myopathy. The entire coding regions of the OCTN2 gene were sequenced in 143 unrelated subjects suspected of having CDSP. In 70 unrelated infants evaluated because of abnormal newborn screening (NBS) results, 48 were found to have at least 1 mutation/unclassified missense variant. Twenty-eight of 33 mothers whose infants had abnormal NBS results were found to carry at least 1 mutation/unclassified missense variant, including 11 asymptomatic mothers who had 2 mutations. Therefore, sequencing of the OCTN2 gene is recommended for infants with abnormal NBS results and for their mothers. Conversely, 52 unrelated subjects were tested due to clinical indications other than abnormal NBS and only 14 of them were found to have at least one mutation/unclassified variant. Custom designed oligonucleotide array CGH analysis revealed a heterozygous ,1.6 Mb deletion encompassing the entire OCTN2 gene in one subject who was apparently homozygous for the c.680G>A (p.R227H) mutation. Thus, copy number abnormalities at the OCTN2 locus should be considered if by sequencing, an apparently homozygous mutation or only one mutant allele is identified. ©2010 Wiley-Liss, Inc. [source]

Mutations in human monoamine-related neurotransmitter pathway genes,

HUMAN MUTATION, Issue 7 2008
Jan Haavik
Abstract Biosynthesis and metabolism of serotonin and catecholamines involve at least eight individual enzymes that are mainly expressed in tissues derived from the neuroectoderm, e.g., the central nervous system (CNS), pineal gland, adrenal medulla, enterochromaffin tissue, sympathetic nerves, and ganglia. Some of the enzymes appear to have additional biological functions and are also expressed in the heart and various other internal organs. The biosynthetic enzymes are tyrosine hydroxylase (TH), tryptophan hydroxylases type 1 and 2 (TPH1, TPH2), aromatic amino acid decarboxylase (AADC), dopamine beta-hydroxylase (D,H), and phenylethanolamine N -methyltransferase (PNMT), and the specific catabolic enzymes are monoamine oxidase A (MAO-A) and catechol O -methyltransferase (COMT). For the TH, DDC, DBH, and MAOA genes, many single nucleotide polymorphisms (SNPs) with unknown function, and small but increasing numbers of cases with autosomal recessive mutations have been recognized. For the remaining genes (TPH1, TPH2, PNMT, and COMT) several different genetic markers have been suggested to be associated with regulation of mood, pain perception, and aggression, as well as psychiatric disturbances such as schizophrenia, depression, suicidality, and attention deficit/hyperactivity disorder. The genetic markers may either have a functional role of their own, or be closely linked to other unknown functional variants. In the future, molecular testing may become important for the diagnosis of such conditions. Here we present an overview on mutations and polymorphisms in the group of genes encoding monoamine neurotransmitter metabolizing enzymes. At the same time we propose a unified nomenclature for the nucleic acid aberrations in these genes. New variations or details on mutations will be updated in the Pediatric Neurotransmitter Disorder Data Base (PNDDB) database (www.bioPKU.org). Hum Mutat 29(7), 891,902, 2008. © 2008 Wiley-Liss, Inc. [source]

Functional effects of mutations identified in patients with Multiminicore disease

IUBMB LIFE, Issue 1 2007
Francesco Zorzato
Abstract Multiminicore disease is a recessive congenital myopathy characterized by the presence of small cores or areas lacking oxidative enzymes, in skeletal muscle fibres. From a clinical point of view, the condition is widely heterogeneous and at least four phenotypes have been identified; genetic analysis has revealed that most patients with the classical form of multiminicore characterized by rigidity of the spine, early onset and respiratory impairment harbour recessive mutations in the SEPN1 gene, whereas the majority of patients belonging to the other categories, including patients with ophthalmoplegia or patients with a phenotype similar to central core disease, carry recessive mutations in the RYR1. In the present review we discuss the most recent findings on the functional effect of mutations in SEPN1 and RYR1 and discuss how they may adversely affect muscle function and lead to the clinical phenotype. IUBMB Life, 59: 14-20, 2007 [source]

Central core disease due to recessive mutations in RYR1 gene: Is it more common than described?

MUSCLE AND NERVE, Issue 5 2007
Patrícia M. Kossugue MS
Abstract Central core disease (CCD) is an autosomal-dominant congenital myopathy, with muscle weakness and malignant hyperthermia (MH) susceptibility. We identified two of nine Brazilian CCD families carrying two mutations in the RYR1 gene. The heterozygous parents were clinically asymptomatic, and patients were mildly affected, differing from the few autosomal-recessive cases described previously. Recessive inheritance in CCD may therefore be more common than previously appreciated, which has important implications for genetic counseling and MH prevention in affected families. Muscle Nerve, 2007 [source]

The VERNALIZATION INDEPENDENCE 4 gene encodes a novel regulator of FLOWERING LOCUS C

THE PLANT JOURNAL, Issue 5 2002
Hua Zhang
Summary The late-flowering, vernalization-responsive habit of many Arabidopsis ecotypes is mediated predominantly through repression of the floral programme by the FLOWERING LOCUS C (FLC) gene. To better understand this repressive mechanism, we have taken a genetic approach to identify novel genes that positively regulate FLC expression. We identified recessive mutations in a gene designated VERNALIZATION INDEPENDENCE 4 (VIP4), that confer early flowering and loss of FLC expression in the absence of cold. We cloned the VIP4 gene and found that it encodes a highly hydrophilic protein with similarity to proteins from yeasts, Drosophila, and Caenorhabditis elegans. Consistent with a proposed role as a direct activator of FLC, VIP4 is expressed throughout the plant in a pattern similar to that of FLC. However, unlike FLC, VIP4 RNA expression is not down-regulated in vernalized plants, suggesting that VIP4 is probably not sufficient to activate FLC, and that VIP4 is probably not directly involved in a vernalization mechanism. Epistasis analysis suggests that VIP4 could act in a separate pathway from previously identified FLC regulators, including FRIGIDA and the autonomous flowering promotion pathway gene LUMINIDEPENDENS. Mutants lacking detectable VIP4 expression flower earlier than FLC null mutants, suggesting that VIP4 regulates flowering-time genes in addition to FLC. Floral morphology is also disrupted in vip4 mutants; thus, VIP4 has multiple roles in development. [source]

Importance of colour in the reaction of passerine predators to aposematic prey: experiments with mutants of Pyrrhocoris apterus (Heteroptera)

BIOLOGICAL JOURNAL OF THE LINNEAN SOCIETY, Issue 1 2006
ALICE EXNEROVÁ
Persistent questions concerning the warning coloration of unpalatable insects address whether the bright aposematic colour itself or its combination with a species-specific dark pattern is the key factor in their protection against insectivorous birds, and how chromatic polymorphism originates and is maintained in aposematics. In the present study, these questions were tested experimentally, using the birds Parus major, Parus caeruleus, Erithacus rubecula, and Sylvia atricapilla as predators, and chromatically polymorphic firebug Pyrrhocoris apterus: red wild form, white, yellow, and orange mutants (all four of them with the same black melanin pattern, the mutants differing in colour of pteridine pigments only) and the nonaposematic brown-painted wild form as prey. The results show that a specific colour is essential for the birds to recognize the specific aposematic prey; the melanin pattern is not sufficient. White mutants were no better protected than nonaposematic firebugs; red wild-type and orange mutants were equally well protected against all bird species; and the reaction of birds to yellow mutants was species-specific. An evolutionary scenario of 'recurrent recessive mutations' is formulated to explain the origin of colour polymorphism in some aposematics. © 2006 The Linnean Society of London, Biological Journal of the Linnean Society, 2006, 88, 143,153. [source]