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Recessive Form (recessive + form)
Kinds of Recessive Form Selected AbstractsGenetic Malformations of the Cerebral Cortex and EpilepsyEPILEPSIA, Issue 2005Renzo Guerrini Summary:, We reviewed the epileptogenic cortical malformations for which a causative gene has been cloned or a linkage obtained. X-linked bilateral periventricular nodular heterotopia (BPNH) consists of typical BPNH with epilepsy in female patients and prenatal lethality in most males. About 90% of patients have focal epilepsy. Filamin A mutations have been reported in all families and in ,20% of sporadic patients. A rare recessive form of BPNH also has been reported. Most cases of lissencephaly,pachygyria are caused by mutations of LIS1 and XLIS genes. LIS1 mutations cause a more severe malformation posteriorly. Most children have isolated lissencephaly, with severe developmental delay and infantile spasms, but milder phenotypes have been recorded. XLIS usually causes anteriorly predominant lissencephaly in male patients and subcortical band heterotopia (SBH) in female patients. Thickness of the band and severity of pachygyria correlate with the likelihood of developing Lennox,Gastaut syndrome. Mutations of the coding region of XLIS are found in all reported pedigrees and in 50% of sporadic female patients with SBH. Autosomal recessive lissencephaly with cerebellar hypoplasia; accompanied by severe delay, hypotonia, and seizures, has been associated with mutations of the RELN gene. Schizencephaly has a wide anatomoclinical spectrum, including focal epilepsy in most patients. Familial occurrence is rare. Initial reports of heterozygous mutations in the EMX2 gene need confirmation. Among several syndromes featuring polymicrogyria, bilateral perisylvian polymicrogyria shows genetic heterogeneity, including linkage to Xq28 in some pedigrees, autosomal recessive inheritance in others, and association with 22q11.2 deletion in some patients. About 65% of patients have severe epilepsy, often Lennox,Gastaut syndrome. Recessive bilateral frontal polymicrogyria has been linked to chromosome 16q12.2,21. [source] Mutations in severe combined immune deficiency (SCID) due to JAK3 deficiencyHUMAN MUTATION, Issue 4 2001Luigi D. Notarangelo Abstract During the last 10 years, an increasing number of genes have been identified whose abnormalities account for primary immunodeficiencies, with defects in development and/or function of the immune system. Among them is the JAK3 -gene, encoding for a tyrosine kinase that is functionally coupled to cytokine receptors which share the common gamma chain. Defects of this gene cause an autosomal recessive form of severe combined immunodeficiency with almost absent T-cells and functionally defective B-cells (T,B+ SCID). Herewith, we present molecular information on the first 27 unique mutations identified in the JAK3 gene, including clinical data on all of the 23 affected patients reported so far. A variety of mutations scattered throughout all seven functional domains of the protein, and with different functional effects, have been identified. Availability of a molecular screening test, based on amplification of genomic DNA, facilitates the diagnostic approach, and has permitted recognition that JAK3 deficiency may also be associated with atypical clinical and immunological features. Development of a structural model of the JAK3 kinase domain has allowed characterization of the functional effects of the various mutations. Most importantly, molecular analysis at the JAK3 locus results in improved genetic counseling, allows early prenatal diagnosis, and prompts appropriate treatment (currently based on hematopoietic stem cell transplantation) in affected families. Hum Mutat 18:255,263, 2001. © 2001 Wiley-Liss, Inc. [source] A Novel Early Onset Lethal Form of Catecholaminergic Polymorphic Ventricular Tachycardia Maps to Chromosome 7p14-p22JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 10 2007Ph.D., ZAHURUL A. BHUIYAN M.D. Introduction: Previously, autosomal dominant catecholaminergic polymorphic ventricular tachycardia (CPVT [1]) was mapped to chromosome 1q42,43 with identification of pathogenic mutations in RYR2. Autosomal recessive CPVT (2) was mapped to chromosome 1p13,21, leading to the identification of mutations in CASQ2. In this study, we aimed to elucidate clinical phenotypes of a new variant of CPVT (3) in an inbred Arab family and also delineate the chromosomal location of the gene causing CPVT (3). Methods and Results: In a highly inbred family, clinical symptoms of CPVT appeared early in childhood (7,12 years) and in three of the four cases, the first appearance of symptoms turned into a fatal outcome. Parents of the affected children were first-degree cousins and without any symptoms. Segregation analysis suggested an autosomal recessive inheritance. A genome-wide search using polymorphic DNA markers mapped the disease locus to a 25-Mb interval on chromosome 7p14-p22. A maximal multipoint LOD score of 3.17 was obtained at marker D7S493. Sequencing of putative candidate genes, SP4, NPY, FKBP9, FKBP14, PDE1C, and TBX20, in and around this locus, did not reveal any mutation. Conclusions: We have identified a novel highly malignant autosomal recessive form of CPVT and mapped this disorder to a 25-Mb interval on chromosome 7p14-p22. [source] Hereditary hypophosphatemias: New genes in the bone,kidney axis (Review Article)NEPHROLOGY, Issue 4 2007ARMANDO L NEGRI SUMMARY: Hypophosphatemia due to isolated renal phosphate wasting is a genetically heterogeneous disease. Two new genes linked to two different forms of hereditary hypophosphatemias have recently been described. Autosomal recessive form of hypophosphatemic rickets was mapped to chromosome 4q21 and identified homozygous mutations in dentin matrix protein 1 (DMP1) gene, which encodes a non-collagenous bone matrix protein. Intact plasma levels of the phosphaturic protein FGF23 (fibroblast growth factor 23) were clearly elevated in some of the affected individuals, providing a possible explanation for the phosphaturia and inappropriately normal 1,25(OH)2D levels, and suggesting that DMP1 may regulate FGF23 expression. Hereditary hypophosphatemic rickets with hypercalciuria is another rare disorder of autosomal recessive inheritance. Affected individuals present with hypercalciuria due to increased serum 1,25-dihydroxyvitamin D levels and increased intestinal calcium absorption. The disease was mapped to a 1.6 Mbp region on chromosome 9q34, which contains SLC34A3, the gene encoding the renal sodium-phosphate cotransporter NaPi-IIc. This was the first demonstration that NaPi-IIc has a key role in the regulation of phosphate homeostasis. Thus, DMP1 and NaPi-IIc add two new members to the bone,kidney axis proposed since it was discovered that the first phosphatonin, FGF23, was of osteoblastic/osteocyte origin. This provides a mechanism for the skeleton to communicate with the kidney to coordinate the mineralization of extracelular matrix and the renal handling of phosphate. [source] Extensive Tinea in a Patient With Severe Combined ImmunodeficiencyPEDIATRIC DERMATOLOGY, Issue 2 2009RAFAEL JIMÉNEZ-PUYA M.D. Although the X-linked recessive form is most common (60,70%), there are autosomal recessive forms (20%) and spontaneous mutations. While SCID may present with many nosocomial infections, dermatophyte infections are not common. We reported a case of SCID which was associated with a widespread skin infection with Trichophyton mentagrophytes. [source] Evaluation of RDS/Peripherin and ROM1 as candidate genes in generalised progressive retinal atrophy and exclusion of digenic inheritanceANIMAL GENETICS, Issue 3 2000M Runte Summary Generalised progressive retinal atrophy (gPRA) is a heterogeneous group of hereditary diseases causing degeneration of the retina in dogs and cats. As a combination of mutations in theRDS/Peripherin and the ROM1 genes leads to the phenotype of retinitis pigmentosa in man we first performed mutation analysis to screen these genes for disease causing mutations followed by the investigation of a digenic inheritance in dogs. We cloned the RDS/Peripherin gene and investigated the RDS/Peripherin and ROM1 genes for disease causing mutations in 13 gPRA-affected dog breeds including healthy animals, obligate gPRA carriers and gPRA-affected dogs. We screened for mutations using single strand conformation polymorphism (SSCP) analysis. Sequence analysis revealed several sequence variations. In the coding region of the RDS/Peripherin gene three nucleotide exchanges were identified (A277C; C316T; G1255A), one of which leads to an amino acid substitution (Ala339Thr). Various silent sequence variations were found in the coding region of the ROM1 gene (A536G, G1006A, T1018C, T1111C, C1150T, C1195T), as well as an amino acid substitution (G252T; Ala54Ser). By excluding the respective gene as a cause for gPRA several sequence variations in the intronic regions were investigated. None of these sequence variations cosegregated with autosomal recessively (ar) transmitted gPRA in 11 breeds. The candidate geneRDS/Peripherin obviously does not harbour the critical mutation causing the autosomal recessive form of gPRA because diseased individuals show heterozygous genotypes for sequence variations in the Miniature Poodle, Dachshund, Australian Cattle Dog, Cocker Spaniel, Chesapeake Bay Retriever, Entlebucher Sennenhund, Sloughi, Yorkshire Terrier, Tibet Mastiff, Tibet Terrier and Labrador Retriever breeds. In the following breeds the ROM1 gene was also excluded indirectly for gPRA: Miniature Poodle, Dachshund, Australian Cattle Dog, Sloughi, Collie, Tibet Terrier, Labrador Retriever and Saarloos/Wolfhound. Digenic inheritance for gPRA is practically excluded for both these genes in four breeds: Miniature Poodle, Dachshund, Labrador Retriever and Saarloos/Wolfhound. [source] A novel deletion mutation in LIPH gene causes autosomal recessive hypotrichosis (LAH2)CLINICAL GENETICS, Issue 2 2008M Jelani Autosomal recessive hypotrichosis is a rare hereditary disorder characterized by sparse hair on scalp and rest of the body of affected subjects. Recently, three clinically similar autosomal recessive forms of hypotrichosis [localized autosomal recessive hypotrichosis (LAH)1], LAH2 and LAH3 have been mapped on chromosomes 18q12.1, 3q27.3, and 13q14.11-q21.32, respectively. For these three loci, two genes DSG4 for LAH1 and LIPH for LAH2 have been identified. To date, only five mutations in DSG4 and two in LIPH genes have been reported. In this study, we have ascertained two large unrelated consanguineous Pakistani families with autosomal recessive form of hypotrichosis. Affected individuals showed homozygosity to the microsatellite markers tightly linked to LIPH gene on chromosome 3q27. Sequence analysis of the gene in the affected subjects from both the families revealed a novel deletion mutation in exon 5 (c.659-660delTA) causing frameshift and downstream premature termination codon. All the three mutations identified in the LIPH gene, including the one in this study, are deletion mutations. [source] Novel COL4A5, COL4A4, and COL4A3 mutations in Alport syndrome,,HUMAN MUTATION, Issue 1 2005Mato Nagel Abstract This study summarizes 47 novel mutations identified during routine molecular diagnostics for Alport syndrome. We detected 34 in COL4A5, the gene responsible for X-linked Alport syndrome, and 13 in COL4A3 and COL4A4, the genes responsible for autosomal recessive Alport syndrome. A high detection rate of 90% was achieved among patients with typical clinical symptoms and a characteristic family history in both X-linked and autosomal recessive forms, and it can be assumed that most relevant mutations have been identified. In numerous positively tested patients, genetic variations which are unknown were detected. © 2005 Wiley-Liss, Inc. [source] Abstracts of the 8th Meeting of the Italian Peripheral Nerve Study Group: 65JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2003E Bellone Mutations in a gene encoding a novel protein of unknown function, the ganglioside-induced differentiation-associated protein 1 gene (GDAP1), are associated with one of the autosomal recessive forms of Charcot-Marie-Tooth disease (CMT4A). Mutations in GDAP1 can cause both axonal and demyelinating inherited peripheral neuropathies. The GDAP1 gene maps on chromosome 8q21.1, encompassing 13.9 kb of genomic DNA. The coding sequence is comprised of six exons. Little is known about the function of GDAP1. The mouse homologue Gdap1 is highly expressed in brain. Northern-blot analysis showed that GDAP1 is also expressed in peripheral nerves, both in neurons and in Schwann cells. A series of Italian patients with demyelinating (n = 42) and axonal (n = 39) peripheral neuropathy with possible recessive inheritance was screened for mutations in the GDAP1 gene. The entire coding region, including exon-intron boundaries, was examined by single strand conformation polymorphism (SSCP) and direct sequencing. All patients were negative for the 17p11.2 duplication and for mutations in the MPZ, GJB1, PMP22 and EGR2 genes. SSCP analysis showed a few electrophoretic variants, in the exon 1, exon 3 and exon 4, respectively. Direct sequencing demonstrated the presence of a common single nucleotide polymorphism in the exon 4 (c.507T > G) and a nucleotide substitution in the exon 3. The latter was found in four patients, belonging to three families, and was not detected in a series of normal subjects. Further studies are in progress to evaluate the possible role of this variant in the pathophysiology of the disease. This work was partially supported by grants MURST 2000 to F.A. and Ministero della Sanità to P.M. [source] Parkinson's disease in Arabs: A systematic reviewMOVEMENT DISORDERS, Issue 9 2008FRCP, Hani T.S. Benamer PhD Abstract Studies of specific populations have provided invaluable knowledge about Parkinson's disease (PD), especially in the field of genetics. The present report systematically reviews the medical literature on PD in Arabs. Medline and Embase were searched, and 24 article were identified: genetic (n = 17), epidemiological (n = 3), and clinical series (n = 5). Both autosomal dominant and recessive forms of inherited PD are described, associated with four genes (Parkin, PINK1, LRRK2, and PARK9). The G2019S LRRK2 mutation is more common in both familial (37,42%) and apparently sporadic PD (41%) in North African Arabs than in Europeans and North Americans (2,3%). The incidence of PD is reported at 4.5 per 100,000 person-years and reported prevalence at 27 to 43 per 100,000 persons. Hospital-based clinical series suggest that parkinsonism is the commonest movement disorder. Clinical features of PD in Arabs are not significantly different from those reported elsewhere. PD was reported as the cause of dementia in around 7% of Arabs. The majority of studies relate to the role of genes in the etiology of PD in North African Arabs. Further genetic, epidemiological and clinical studies from the majority of Arabic countries may enhance our understanding of PD. © 2008 Movement Disorder Society. [source] The dominantly inherited motor and sensory neuropathies: Clinical and molecular advancesMUSCLE AND NERVE, Issue 5 2006Garth A. Nicholson MB Abstract The rapid advances in the molecular genetics and cell biology of hereditary neuropathy have revealed great genetic complexity. It is a challenge for physicians and laboratories to keep pace with new discoveries. Classification of hereditary neuropathies has evolved from a simple clinical to a detailed molecular classification. However, the molecular classification is not simple to use, as different mutations of the same gene produce a range of phenotypes. The logistics of testing for multiple gene mutations are considerable. This review gives a clinical overview of molecular and clinical advances in the dominant hereditary motor and sensory neuropathies [HMSNs, Charcot,Marie,Tooth (CMT) neuropathy], which account for some 60%,70% of families with CMT. The dominant forms of CMT have cellular mechanisms different from those of recessive forms and are a separate diagnostic challenge, so they are not included in this review. Diagnostic testing requires accurate clinical information and a selective approach to gene screening until the cost of multiple gene mutation screening falls. Accurate molecular diagnosis is critical to genetic counseling. This review concentrates on how molecular information can be used clinically, on how physicians can keep pace with new developments, and on the relevance of this new knowledge to patients. Muscle Nerve, 2006 [source] Extensive Tinea in a Patient With Severe Combined ImmunodeficiencyPEDIATRIC DERMATOLOGY, Issue 2 2009RAFAEL JIMÉNEZ-PUYA M.D. Although the X-linked recessive form is most common (60,70%), there are autosomal recessive forms (20%) and spontaneous mutations. While SCID may present with many nosocomial infections, dermatophyte infections are not common. We reported a case of SCID which was associated with a widespread skin infection with Trichophyton mentagrophytes. [source] High frequency of the 425A,G splice-site mutation and novel mutations of the COL7A1 gene in central Europe: significance for future mutation detection strategies in dystrophic epidermolysis bullosaBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2005M. Csikós Summary Background, Mutations in the type VII collagen gene (COL7A1) are responsible for dominant and recessive forms of dystrophic epidermolysis bullosa (DEB). These mutations are usually specific for individual families; only a few cases of recurring mutations have been identified. Objectives, Forty-three unrelated Hungarian and German patients with different DEB phenotypes were screened for novel and recurrent COL7A1 mutations. Methods, All patients were classified based on clinical and genetic findings, skin immunofluorescent antigen mapping, and electron microscopic studies. Mutation analysis was performed by amplification of genomic DNA with polymerase chain reaction using COL7A1 -specific primers, heteroduplex analysis, and direct nucleotide sequencing. Restriction endonuclease digestion was used for family screening and mutation verification. Results, In this group of patients, the splice-site mutation 425A,G was observed frequently, in 11 of 86 alleles (12·8%), once in homozygous form and in nine cases in heterozygous form. One of 100 control alleles from clinically unaffected individuals also carried the mutation. We also identified three novel mutations: the 976-3C,A splice-site mutation, and the 4929delT and 8441-15del20 deletions. Conclusions, High recurrence of the splice-site mutation 425A,G in central European patients with DEB should be taken into account when designing COL7A1 mutation detection strategies. Reporting of three novel COL7A1 mutations in this study further emphasizes the molecular heterogeneity of DEB and provides more information for studies on genotype,phenotype correlations in different DEB subtypes. [source] A novel deletion mutation in LIPH gene causes autosomal recessive hypotrichosis (LAH2)CLINICAL GENETICS, Issue 2 2008M Jelani Autosomal recessive hypotrichosis is a rare hereditary disorder characterized by sparse hair on scalp and rest of the body of affected subjects. Recently, three clinically similar autosomal recessive forms of hypotrichosis [localized autosomal recessive hypotrichosis (LAH)1], LAH2 and LAH3 have been mapped on chromosomes 18q12.1, 3q27.3, and 13q14.11-q21.32, respectively. For these three loci, two genes DSG4 for LAH1 and LIPH for LAH2 have been identified. To date, only five mutations in DSG4 and two in LIPH genes have been reported. In this study, we have ascertained two large unrelated consanguineous Pakistani families with autosomal recessive form of hypotrichosis. Affected individuals showed homozygosity to the microsatellite markers tightly linked to LIPH gene on chromosome 3q27. Sequence analysis of the gene in the affected subjects from both the families revealed a novel deletion mutation in exon 5 (c.659-660delTA) causing frameshift and downstream premature termination codon. All the three mutations identified in the LIPH gene, including the one in this study, are deletion mutations. [source] | |||||||||||||||||||||||||