The Department of Endocrinology, 
Low genetic confirmation rate in South Indian subjects with a clinical diagnosis of maturity-onset diabetes of the young (MODY) who underwent targeted next-generation sequencing for 13 genes.
- Department of Endocrinology, Amrita Institute of Medical Sciences, Amrita University, Ponnekara P.O, Cochin, 682041, Kerala, India.
- Department of Endocrinology, Amrita Institute of Medical Sciences, Amrita University, Ponnekara P.O, Cochin, 682041, Kerala, India. pravvp@gmail.com.
- Department of Endocrinology, Christian Medical College, Vellore, Tamil Nadu, India.
Journal of endocrinological investigation Vol. 45 · Issue 3 · pp. 607-615
PMID 34741762 DOI 10.1007/s40618-021-01698-y
Cite This Article
G Sampathkumar, P P Valiyaparambil, H Kumar, N Bhavani, V Nair, U Menon, A Menon, N Abraham, A Chapla, N Thomas. Low genetic confirmation rate in South Indian subjects with a clinical diagnosis of maturity-onset diabetes of the young (MODY) who underwent targeted next-generation sequencing for 13 genes. Journal of endocrinological investigation. 2022;45(3):607-615. doi:10.1007/s40618-021-01698-y
Abstract
PURPOSE: To screen for maturity-onset diabetes of the young (MODY) variants in subjects with an early age of onset and positive family history of diabetes mellitus.
METHODS: 60 subjects with onset of diabetes between 3 and 30 years of age and parental history (onset
RESULTS: Baseline characteristics of subjects were as follows: mean age of onset of diabetes 19.9 ± 7 years, mean duration of diabetes 6.3 ± 6.8 years, BMI 23.3 ± 3 kg/m and C-peptide 1.56 ± 1.06 nmol/l. Four out of sixty (6.6%) were positive for variants classifiable as pathogenic/likely pathogenic: one patient with HNF4Ac.691C > T, (p.Arg231Trp), two with HNF 1A c.746C > A(p.Ser249Ter) and c.1340C > T(p.Pro447Leu), and one with ABCC8 c.4544C > T (p.Thr1515Met). MODY 1 and MODY 3 variants were documented in the paediatric age group (
CONCLUSION: A genetic diagnosis of MODY could be confirmed in only 6.6% (4/60) of patients clinically classifiable as MODY. This is less than that reported in clinically diagnosed MODY subjects of European descent. Newly published population data and more stringent criteria for assessment of pathogenicity and younger age of onset of type 2 diabetes in Indians could have contributed to the lower genetic confirmation rate. Apart from variants in the classical genes (HNF1A, HNF4A), a likely pathogenic variant in a non-classical gene (ABCC8) was noted in this study.
Keywords
- C-peptide
- Maturity-onset diabetes of the young (MODY)
- Mutations
- Next-generation sequencing (NGS)
- Phenotype
- Prevalence
