Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Ano de publicação
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Medicina (Kaunas) ; 60(1)2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38256360

RESUMO

Background and Objectives: Danon disease is a multisystemic disorder associated with variants in the LAMP2 gene, mainly affecting the cardiac muscle. Here, we report a multigenerational family from Latvia with two male patients, hemizygous for a novel splice-affecting variant c.928+3A>G. Affected patients exhibit a cardiac phenotype, moderate mental disability, and mild retinal changes. Materials and Methods: Both patients underwent either exome or hypertrophic cardiomyopathy gene panel next-generation sequencing. The pathogenic variant effect was determined using reverse transcription, Sanger sequencing, and high-resolution electrophoresis. Results: Evaluation of the splicing process revealed that approximately 80% of the transcripts exhibited a lack of the entire exon 7. This alteration was predicted to cause a shift of the reading frame, consequently introducing a premature stop codon downstream in the sequence. Conclusions: Based on our data, we propose that c.928+3A>G is a pathogenic variant associated with Danon disease.


Assuntos
Doença de Depósito de Glicogênio Tipo IIb , Humanos , Masculino , Doença de Depósito de Glicogênio Tipo IIb/genética , Família Estendida , Letônia , Miocárdio , Genes Reguladores , Proteína 2 de Membrana Associada ao Lisossomo/genética
2.
Hum Mutat ; 43(10): 1347-1353, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35731190

RESUMO

The investigated intronic CAPN3 variant NM_000070.3:c.1746-20C>G occurs in the Central and Eastern Europe with a frequency of >1% and there are conflicting interpretations on its pathogenicity. We collected data on 14 patients carrying the CAPN3 c.1746-20C>G variant in trans position with another CAPN3 pathogenic/likely pathogenic variant. The patients compound heterozygous for the CAPN3 c.1746-20C>G variant presented a phenotype consistent with calpainopathy of mild/medium severity. This variant is most frequent in the North/West regions of Russia and may originate from that area. Molecular studies revealed that different splicing isoforms are produced in the muscle. We hypothesize that c.1746-20C>G is a hypomorphic variant with a reduction of RNA and protein expression and only individuals having a higher ratio of abnormal isoforms are affected. Reclassification of the CAPN3 variant c.1746-20C>G from variant with a conflicting interpretation of pathogenicity to hypomorphic variant explains many unidentified cases of limb girdle muscular dystrophy R1 calpain 3-related in Eastern and Central Europe.


Assuntos
Calpaína , Proteínas Musculares , Distrofia Muscular do Cíngulo dos Membros , Calpaína/genética , Humanos , Proteínas Musculares/genética , Distrofia Muscular do Cíngulo dos Membros/genética , Mutação , Splicing de RNA
3.
Front Genet ; 13: 780764, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35222531

RESUMO

There are recent reports of associations of variants in the HPDL gene with a hereditary neurological disease that presents with a wide spectrum of clinical severity, ranging from severe neonatal encephalopathy with no psychomotor development to adolescent-onset uncomplicated spastic paraplegia. Here, we report two probands from unrelated families presenting with severe and intermediate variations of the clinical course. A homozygous variant in the HPDL gene was detected in each proband; however, there was no known parental consanguinity. We also highlight reductions in citrate synthase and mitochondrial complex I activity detected in both probands in different tissues, reflecting the previously proposed mitochondrial nature of disease pathogenesis associated with HPDL mutations. Further, we speculate on the functional consequences of the detected variants, although the function and substrate of the HPDL enzyme are currently unknown.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA