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1.
Meta Gene ; 2: 25-31, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25606386

RESUMO

Craniofrontonasal syndrome (CFNS) is an X-linked disorder caused by mutations in the EFNB1 gene and characterized by distinctive craniofacial and digital malformations. In contrast with most X-linked traits, female patients with CFNS display a more severe phenotype than males. In this report, the clinical, molecular and RNA expression analyses of a female subject with CFNS are described. A novel c.445_449delGAGGG deletion in exon 3 of EFNB1 was demonstrated in this patient. To assess the effect of this novel mutation at the transcript level, the expression of EFNB1 mRNA was studied by quantitative RT-PCR. To our knowledge, this is the first time that an EFNB1 transcript carrying a truncating mutation in exon 3 is demonstrated to undergo degradation by nonsense-mediated mRNA decay. Our results expand the mutational spectrum of CFNS and add to the functional consequences of truncating EFNB1 mutations.

2.
Exp Eye Res ; 109: 77-82, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23419329

RESUMO

The aim of this study was to assess the mutational spectrum of the ABCA4 gene in a cohort of patients with Stargardt disease from Mexico, a previously uncharacterized population. Clinical diagnosis in each patient was supported by a complete ophthalmological assessment that included visual acuity measurement, a slit lamp examination, a fundus examination and photography, electroretinography, fluorescein angiography, and computerized visual fields testing. Molecular analysis was performed by PCR amplification and direct nucleotide sequence of the 50 exons of the ABCA4 gene in genomic DNA. A total of 31 unrelated subjects with the disease were enrolled in the study. Molecular analysis in the total group of 62 alleles allowed the identification of 46 mutant ABCA4 alleles carrying 29 different pathogenic disease-associated mutations. Two ABCA4 mutant alleles were detected in 20 of the 31 patients (64.5%), a single disease allele was identified in six (19.4%), and no mutant alleles were detected in five of the cases (16.1%). Most patients with two ABCA4 mutations (11/20, 55%) were compound heterozygotes. Twelve variants were novel ABCA4 mutations. Nucleotide substitutions were the most frequent type of variation, occurring in 26 out of 29 (89.7%) different mutations. The two most common mutations in our study were the missense changes p.A1773V and p.G818E, which were identified in eight (17%) and seven (15%) of the total 46 disease-associated alleles, respectively. Haplotype analyses of intragenic SNPs in four subjects carrying the p.A1773V mutation supported a common origin for this mutation. In conclusion, this is the first report of ABCA4 molecular screening in Latin American Stargardt disease patients. Our results expand the mutational spectrum of the disease by adding 12 novel ABCA4 pathogenic variants and support the occurrence of a founder effect for the p.A1773V mutation in the Mexican population. The identification of recurrent mutations in our cohort will direct future ABCA4 molecular screening in patients from this ethnic group.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Degeneração Macular/etnologia , Degeneração Macular/genética , Distrofias Retinianas/etnologia , Distrofias Retinianas/genética , Adolescente , Adulto , Criança , Análise Mutacional de DNA , Feminino , Efeito Fundador , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Heterozigoto , Homozigoto , Humanos , Masculino , México/epidemiologia , Mutação Puntual , Adulto Jovem
3.
Ophthalmic Genet ; 34(4): 243-8, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23373429

RESUMO

PURPOSE: To present the results of the clinical and molecular analyses of a familial case of Wolfram Syndrome (WFS) associated with a novel ocular anomaly. METHODS: Full ophthalmologic examination was performed in two WFS siblings. Visante OCT imaging was used for assessing anterior segment anomalies. Genetic analysis included PCR amplification and exon-by-exon nucleotide sequencing of the WFS1 gene. RESULTS: Ocular anomalies in both affected siblings included congenital cataract, glaucoma, and optic atrophy. Interestingly, microspherophakia, a feature that has not been previously associated with WFS, was observed in both siblings. Genetic analysis disclosed a novel c.1525_1539 homozygous deletion in exon 8 of WFS1 in DNA from both affected patients. CONCLUSIONS: The recognition of microspherophakia in two siblings carrying a novel WFS1 mutation expands the clinical and molecular spectrum of Wolfram syndrome.


Assuntos
Cromossomos Humanos Par 4/genética , Anormalidades do Olho/genética , Cristalino/anormalidades , Proteínas de Membrana/genética , Deleção de Sequência , Síndrome de Wolfram/genética , Adolescente , Sequência de Bases , Éxons/genética , Anormalidades do Olho/diagnóstico , Feminino , Humanos , Dados de Sequência Molecular , Linhagem , Reação em Cadeia da Polimerase , Irmãos , Tomografia de Coerência Óptica , Síndrome de Wolfram/diagnóstico , Adulto Jovem
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