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Entire Gene (entire + gene)
Selected AbstractsIdentification of forty-five novel and twenty-three known NF1 mutations in Chinese patients with neurofibromatosis type 1,,HUMAN MUTATION, Issue 8 2006Ming-Jen Lee Abstract Neurofibromatosis type 1 (NF1), characterized by skin neurofibromas and an excess of café-au-lait spots, is due to mutations in the neurofibromin (NF1) gene. Identifying the genetic defect in individuals with the disease represents a significant challenge because the gene is extremely large with a high incidence of sporadic mutations across the entire gene ranging from single nucleotide substitutes to large deletions. In the present study, we have used a combination of techniques (heteroduplex analysis, sequencing, loss of heterozygosity and quantification of gene dosage) to define the genetic defect in 68 individuals from a cohort of 107 NF1 Taiwanese patients of Chinese origin. Fifty-eight were initially identified using heteroduplex analytical techniques and confirmed by sequence analysis. A further five were identified by direct sequence analysis alone. The reminders were shown to carry large deletions in the NF1 gene by demonstrating loss of heterozygosity that was confirmed by gene dosage measurements using quantitative-PCR techniques. Mis-sense, non-sense, frame-shift or splice-site mutations were identified across the entire gene of which the majority (45/68) were novel in nature. The detection rate with the various analytical techniques and the types of mutation detected are consistent with published data involving both individuals and large cohort studies from other ethnic backgrounds. © 2006 Wiley-Liss, Inc. [source] Prenatal diagnosis of 21-hydroxylase deficiency caused by gene conversion and rearrangements: pitfalls and molecular diagnostic solutionsPRENATAL DIAGNOSIS, Issue 13 2002Rong Mao Abstract Objectives The present paper reports the prenatal diagnosis of congenital adrenal hyperplasia (CAH) in two cases of 21-hydroxylase deficiency. DNA diagnostic errors can be caused by the presence of the highly homologous 21-hydroxylase pseudogene, CYP21P, adjacent to the functional gene, CYP21. The present paper details how complex gene conversions and rearrangements between the CYP21 and CYP21P pose unique complications for prenatal diagnosis. Methods Analysis of eight common mutations in the 21-hydroxylase gene as well as deletion of the entire gene is accomplished using polymerase chin reaction (PCR) followed by amplified created restriction site (ACRS) or allele-specific oligohybridization (ASO) and Southern blot followed by hybridization to a CYP21-specific probe. Linkage analysis was performed using microsatellite markers flanking the CYP21 gene. Results The direct mutation detection assay indicated a complicated gene conversion and rearrangement in the probands of both families. Interpretation of these rearrangements made it difficult to determine whether or not the fetuses would be affected with CAH. Linkage studies revealed that each fetus had inherited both parental disease chromosomes and was therefore predicted to be affected with CAH. Conclusion As observed in the two reported cases, direct DNA analysis may provide limited information due to gene conversion or rearrangement between the CYP21 and CYP21P genes. These cases suggest that direct mutation detection should be supported by linkage analysis, whenever possible, to provide more comprehensive information for the family. Copyright © 2002 John Wiley & Sons, Ltd. [source] Population genetic studies of Alouatta caraya (Alouattinae, Primates): inferences on geographic distribution and ecologyAMERICAN JOURNAL OF PRIMATOLOGY, Issue 10 2007Fabrícia F. Do Nascimento Abstract Cytochrome b DNA sequence data (ca. 1,140,bp) of 44 Alouatta caraya, including 42 specimens from three localities of Brazil and two from Bolivia, were used for phylogenetic reconstructions and population studies. Seventeen haplotypes were identified, eight of which were present in more than one individual. Seven of these eight haplotypes were shared by individuals from a same locality and one by individuals from two localities. We found 26 variable sites along the entire gene, consisting of 18 transitions and eight transversions; most replacements occurring at the third codon position (65.39%) in contrast to first and second positions (26.92 and 7.69%, respectively). In the sample collected at Chapada dos Guimarães (Brazil), nucleotide and haplotype diversity estimates were ,=0.002325 and h=0.8772, respectively. Maximum parsimony analysis grouped all haplotypes in two clades, separating Bolivian haplotypes from Brazilian haplotypes, the grouping of which did not show a straightforward correspondence with geographic distribution. Median-joining and TCS network pointed to haplotypes 11 or 12 as the most likely ancestral ones. Mismatch distribution and the goodness-of-fit test (SSD estimate=0.0027; P=0.6999) indicated that the population from Chapada dos Guimarães experienced a demographic expansion, in agreement with the median-joining star-like pattern, although this finding could not be confirmed by Fu's Fs test. Am. J. Primatol. 69:1093,1104, 2007. © 2007 Wiley-Liss, Inc. [source] De novo duplication of MECP2 in a girl with mental retardation and no obvious dysmorphic featuresCLINICAL GENETICS, Issue 2 2010P Makrythanasis Makrythanasis P, Moix I, Gimelli S, Fluss J, Aliferis K, Antonarakis SE, Morris MA, Béna F, Bottani A. De novo duplication of MECP2 in a girl with mental retardation and no obvious dysmorphic features. Loss-of-function mutations of MECP2 are responsible for Rett syndrome (RTT), an X-linked neurodevelopmental disorder affecting mainly girls. The availability of MECP2 testing has led to the identification of such mutations in girls with atypical RTT features and the recognition of milder forms. Furthermore, duplication of the entire gene has recently been described in boys with mental retardation and recurrent infections. We describe a girl with a heterozygous de novo MECP2 duplication. The patient, at the age of 19, has mental retardation with no autistic features. She is friendly but gets frequently anxious. She has neither dysmorphic features nor malformations. Her motor development was delayed with walking at 20 months. Speech is fluid with good pronunciation but is simple and repetitive. Diagnosis was made after single-strand conformation analysis (SSCA) and multiplex ligation-dependent probe amplification (MLPA) analysis of MECP2. Array comparative genomic hybridization (aCGH) analysis showed a duplication of 29 kb including MECP2 and part of IRAK1. Fluorescent in situ hybridization (FISH) has revealed that the duplicated region is inserted near the telomere of the short arm of chromosome 10. X-chromosome inactivation in leukocyte DNA was not skewed. We conclude that it is likely that this MECP2 duplication is responsible for the mental retardation in this patient. This case broadens the phenotypic spectrum of MECP2 abnormalities with consequent implication in diagnosis and genetic counselling of girls with non-syndromic mental retardation. [source] Genotypic analysis of genes associated with isoniazid and ethionamide resistance in MDR-TB isolates from ThailandCLINICAL MICROBIOLOGY AND INFECTION, Issue 4 2010S. Boonaiam Clin Microbiol Infect 2010; 16: 396,399 Abstract Nucleotide sequences of genes conferring isoniazid resistance (katG, inhA, oxyR,ahpC and ndh) and ethionamide resistance (ethA) in 160 drug-resistant Mycobacterium tuberculosis clinical isolates from Thailand were analysed. Mutations in the katG gene were found in 129 isolates, predominantly at codon 315, which was mutated in 127 isolates. Twenty-two isolates had mutations in the inhA promoter and coding region. Mutations in the oxyR,ahpC intergenic region and in ndh were detected in four and one isolate(s), respectively. Of 24 ethionamide-resistant isolates, 13 had mutations in the ethA gene. However, these mutations were dispersed along the entire gene, with no codon predominating significantly. [source] Mitral valve prolapse and abnormalities of haemostasis in children and adolescents with migraine with aura and other idiopathic headaches: a pilot studyACTA NEUROLOGICA SCANDINAVICA, Issue 2 2010C. Termine Termine C, Trotti R, Ondei P, Gamba G, Montani N, Gamba A, De Simone M, Marni E, Balottin U. Mitral valve prolapse and abnormalities of haemostasis in children and adolescents with migraine with aura and other idiopathic headaches: a pilot study. Acta Neurol Scand: 2010: 122: 91,96. © 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective,,, To investigate the prevalence of mitral valve prolapse (MVP) and abnormalities of haemostasis in children and adolescents with migraine with aura (MA) compared with peers affected by other idiopathic headaches. Materials and methods,,, We recruited 20 MA patients (10 men and 10 women; age range 8,17 years) and 20 sex- and age-matched subjects with other idiopathic headaches. Both groups underwent colour Doppler transthoracic echocardiography to detect MVP and the following laboratory work-up: plasma prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, protein C, protein S, homocysteine, lupus anticoagulant, von Willebrand factor (vWF) ristocetin cofactor activity, immunoglobulins (Ig) G and M anticardiolipin antibodies (aCL). Factor V Leiden, factor II and methylenetetrahydrofolate reductase were investigated (we did not test the entire genes, but screened for specific point mutations). Results,,, The prevalence of MVP was significantly higher in the MA subjects than in the patients affected by other idiopathic headaches (40% vs 10%; P < 0.05). Moreover, the MA patients showed a higher rate of above-normal IgM aCL titres (45% vs 10%; P < 0.05). Finally, in the group of patients with MVP we found a higher prevalence of aCL in those with MA compared with those affected by other idiopathic headaches. Conclusions,,, A proportion, at least, of the MA patients showed a more complex phenotype characterized by MVP and/or positive aCL titres. The pathogenetic role of these associations is obscure and larger studies are needed to confirm the usefulness of echocardiographic and laboratory investigations in this area and to identify possible new treatment approaches that might be explored in this group of MA patients. 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