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WFS1 Gene-associated Diabetes Phenotypes and Identification of a Founder Mutation in Southern India.
Chapla, Aaron; Johnson, Jabasteen; Korula, Sophy; Mohan, Nisha; Ahmed, Anish; Varghese, Deny; Rangasamy, Parthiban; Ravichandran, Lavanya; Jebasingh, Felix; Kumar Agrawal, Krishna; Somasundaram, Noel; Hesarghatta Shyamasunder, Asha; Mathai, Sarah; Simon, Anna; Jha, Sujeet; Chowdry, Subhankar; Venkatesan, Radha; Raghupathy, Palany; Thomas, Nihal.
Afiliação
  • Chapla A; Christian Medical College Vellore, India.
  • Johnson J; Christian Medical College Vellore, India.
  • Korula S; Christian Medical College Vellore, India.
  • Mohan N; Moulana Hospital, Mallapuram, India.
  • Ahmed A; Moulana Hospital, Mallapuram, India.
  • Varghese D; Christian Medical College Vellore, India.
  • Rangasamy P; Christian Medical College Vellore, India.
  • Ravichandran L; Christian Medical College Vellore, India.
  • Jebasingh F; Christian Medical College Vellore, India.
  • Kumar Agrawal K; BP Koirala Institute of Health Sciences, Nepal.
  • Somasundaram N; The National Hospital of Srilanka, Colombo, Srilanka.
  • Hesarghatta Shyamasunder A; Christian Medical College Vellore, India.
  • Mathai S; Christian Medical College Vellore, India.
  • Simon A; Christian Medical College Vellore, India.
  • Jha S; Max Super Speciality Hospital, New Delhi, India.
  • Chowdry S; Institute of Post-Graduate Medical Education and Research, Kolkotta, India.
  • Venkatesan R; Madras Diabetes Research Foundation, Chennai, India.
  • Raghupathy P; Sagar Hospitals, Bengaluru, India.
  • Thomas N; Christian Medical College Vellore, India.
J Clin Endocrinol Metab ; 107(5): 1328-1336, 2022 04 19.
Article em En | MEDLINE | ID: mdl-35018440
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Limite: Female / Humans / Male País/Região como assunto: Asia Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Diagnostic_studies / Prognostic_studies / Risk_factors_studies / Screening_studies Limite: Female / Humans / Male País/Região como assunto: Asia Idioma: En Ano de publicação: 2022 Tipo de documento: Article