RESUMO
Neuronal ceroid lipofuscinosis type 6 (NCL 6) is a rare progressive neurodegenerative disease that belongs to the group of lysosomal storage diseases. A clinical and genetic description of NCL 6 in a Yakut family was carried out. The proband and her sibling showed characteristic clinical signs, including myoclonic epilepsy, ataxia, psychomotor regression, dementia, and visual impairment. The onset of the disease in the age range from 3-4 years. The disease is caused by the frameshift mutation c.396dupT (p.Val133CysfsTer18) in exon 4 of the CLN6 in a homozygous state, which was detected using targeted next generation sequencing. Diagnosis of NCL is difficult due to the pronounced genetic heterogeneity of the disease, as well as the similarity with other hereditary metabolic diseases in clinical manifestations. The method of DNA diagnostics of NCL type 6 using NGS and direct sequencing according to Sanger has been introduced into the practice of medical genetic counseling.
Assuntos
Lipofuscinoses Ceroides Neuronais , Pré-Escolar , Feminino , Homozigoto , Humanos , Proteínas de Membrana/genética , Mutação , Lipofuscinoses Ceroides Neuronais/diagnóstico , Lipofuscinoses Ceroides Neuronais/genéticaRESUMO
This paper reports the first case of cochlear implantation performed in this country in a child with congenital non-syndromic sensorineural loss of hearing having hereditary etiology and attributable to autosomal-recessive 35 delG mutation in locus DFNB1 (13q.11-q12) of GJB2 (connexin 26) gene.
Assuntos
Implante Coclear/métodos , Conexinas/genética , DNA/genética , Predisposição Genética para Doença , Perda Auditiva Neurossensorial/cirurgia , Mutação , Pré-Escolar , Conexina 26 , Análise Mutacional de DNA , Perda Auditiva Neurossensorial/congênito , Perda Auditiva Neurossensorial/genética , Humanos , Masculino , LinhagemRESUMO
The clinical-genealogic and molecular-genetic investigation of oculopharyngeal muscular dystrophy (OPMD) in the Republic of Sakha (Yakutia) was performed. It was investigated 33 unrelated Yakut families with 38 patients and 2 russian families with 2 patients and 59 their healthy relatives as well. The high clinical polymorphism of disease was found in patients with OPMD. The mutation in exon 1 of the PABPN1 gene resulting in the expansion of GCG-repeats up to 10 is revealed. Using direct sequencing of the PABPN1 gene in 17 families (16 Yakut, 1 Russian), we identified a type of this mutation as an insertion of 4 GCG-repeats. Frequency of OPMD in the Yakut population is 1:11 680 that is 10-20 times higher comparing to european populations. This is a first report on the patients with OPMD from the Republic of Sakha with diagnosis confirmed by molecular-genetic analysis.
