WFS1 Gene-associated Diabetes Phenotypes and Identification of a Founder Mutation in Southern India.
J Clin Endocrinol Metab
; 107(5): 1328-1336, 2022 04 19.
Article
em En
| MEDLINE
| ID: mdl-35018440
ABSTRACT
CONTEXT Wolfram syndrome (WFS) is a rare autosomal recessive disorder characterized by juvenile-onset diabetes, diabetes insipidus, optic atrophy, deafness, and progressive neurodegeneration. However, due to the progressive nature of the disease and a lack of complete clinical manifestations, a confirmed diagnosis of WFS at the time of onset of diabetes is a challenge. OBJECTIVE:
With WFS1 rare heterozygous variants reported in diabetes, there is a need for comprehensive genetic screening strategies for the early diagnosis of WFS and delineating the phenotypic spectrum associated with the WFS1 gene variants in young-onset diabetes.METHODS:
This case series of 11 patients who were positive for WFS1 variants were identified with next-generation sequencing (NGS)-based screening of 17 genemonogenic diabetes panel. These results were further confirmed with Sanger sequencing.RESULTS:
9 out of 11 patients were homozygous for pathogenic/likely pathogenic variants in the WFS1 gene. Interestingly, 3 of these probands were positive for the novel WFS1 (NM_006005.3) c.1107_1108insA (p.Ala370Serfs*173) variant, and haplotype analysis suggested a founder effect in 3 families from Southern India. Additionally, we identified 2 patients with young-onset diabetes who were heterozygous for a likely pathogenic variant or a variant of uncertain significance in the WFS1 gene.CONCLUSION:
These results project the need for NGS-based parallel multigene testing as a tool for early diagnosis of WFS and identify heterozygous WFS1 variants implicated in young-onset diabetes.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Wolfram
/
Proteínas de Membrana
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Screening_studies
Limite:
Female
/
Humans
/
Male
País/Região como assunto:
Asia
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Índia