Browsing by Author "Vijayalakshmi Bhatia"

Now showing 1 - 4 of 4

Characterisation of islet antibody-negative type 1 diabetes mellitus in Indian children
(John Wiley and Sons Inc, 2025) Jayakrishnan C. Menon; Pratibha Singh; Archana Archana; Uma Kanga; Preeti Lata Singh; Medha Mittal; Atul Garg; Anju Seth; Vijayalakshmi Bhatia; Preeti Dabadghao; Siddhnath Sudhanshu; Ruchira Vishwakarma; Shivendra Verma; Shipra Kumar Singh; Eesh Bhatia
Aims: Islet antibody-negative type 1 diabetes mellitus (T1DM) has not been well characterised. We determined the frequency of antibody-negative T1DM and compared it with antibody-positive T1DM in a cohort of north Indian children. Methods: In a multi-centre, prospective, observational study, 176 Indian children (age 1–18 years) were assessed within 2 weeks of diagnosis of T1DM. Antibodies against GAD65 (GADA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A), were estimated using validated ELISA. HLA-DRB1, DQA1 and DQB1 alleles were studied by Luminex-based typing. Monogenic diabetes was determined by targeted next-generation sequencing using the Illumina platform. Results: After excluding 12 children with monogenic diabetes, GADA, IA-2A and ZnT8A were present in 124 (76%), 60 (37%) and 62 (38%) children, respectively, while 24 (15%) were negative for all antibodies. A single antibody (most frequently GADA) was present in 68 (41%) of children, while all three antibodies were found in 34 (21%). Islet antibody-negative T1DM (n = 24, 15%) did not differ from antibody-positive children in their clinical features, HbA1c or plasma C-peptide, both at onset or after 1 year follow-up (available in 62 children). The frequency of other organ-specific antibodies or high-risk HLA-DR and DQ alleles were also similar. Children with a single islet antibody did not differ from those with multiple antibodies. Conclusions: The frequency of various islet-antibodies, in isolation and combination, differed considerably from studies among children of European descent with T1DM. Children with T1DM who were islet antibody-negative were indistinguishable from those who were antibody-positive. © 2024 Diabetes UK.
Characterisation of islet antibody-negative type 1 diabetes mellitus in Indian children
(John Wiley and Sons Inc, 2024) Jayakrishnan C. Menon; Pratibha Singh; Archana Archana; Uma Kanga; Preeti Singh; Medha Mittal; Atul Garg; Anju Seth; Vijayalakshmi Bhatia; Preeti Dabadghao; Siddhnath Sudhanshu; Ruchira Vishwakarma; Shivendra Verma; S.K. Singh; Eesh Bhatia
Aims: Islet antibody-negative type 1 diabetes mellitus (T1DM) has not been well characterised. We determined the frequency of antibody-negative T1DM and compared it with antibody-positive T1DM in a cohort of north Indian children. Methods: In a multi-centre, prospective, observational study, 176 Indian children (age 1–18 years) were assessed within 2 weeks of diagnosis of T1DM. Antibodies against GAD65 (GADA), islet antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A), were estimated using validated ELISA. HLA-DRB1, DQA1 and DQB1 alleles were studied by Luminex-based typing. Monogenic diabetes was determined by targeted next-generation sequencing using the Illumina platform. Results: After excluding 12 children with monogenic diabetes, GADA, IA-2A and ZnT8A were present in 124 (76%), 60 (37%) and 62 (38%) o children, respectively, while 24 (15%) were negative for all antibodies. A single antibody (most frequently GADA) was present in 68 (41%) of children, while all three antibodies were found in 34 (21%). Islet antibody-negative T1DM (n = 24, 15%) did not differ from antibody-positive children in their clinical features, HbA1c or plasma C-peptide, both at onset or after 1 year follow-up (available in 62 children). The frequency of other organ-specific antibodies or high-risk HLA-DR and DQ alleles were also similar. Children with a single islet antibody did not differ from those with multiple antibodies. Conclusions: The frequency of various islet-antibodies, in isolation and combination, differed considerably from studies among children of European descent with T1DM. Children with T1DM who were islet antibody-negative were indistinguishable from those who were antibody-positive. © 2024 Diabetes UK.
High Frequency of Recessive WFS1 Mutations Among Indian Children With Islet Antibody-negative Type 1 Diabetes
(Endocrine Society, 2024) Jayakrishnan C Menon; Pratibha Singh; Archana Archana; Preeti Singh; Medha Mittal; Uma Kanga; Kausik Mandal; Anju Seth; Vijayalakshmi Bhatia; Preeti Dabadghao; Siddhnath Sudhanshu; Atul Garg; Ruchira Vishwakarma; Aditya Narayan Sarangi; Shivendra Verma; Surya Kumar Singh; Eesh Bhatia
Background: While the frequency of islet antibody-negative (idiopathic) type 1 diabetes mellitus (T1DM) is reported to be increased in Indian children, its aetiology has not been studied. We investigated the role of monogenic diabetes in the causation of islet antibody-negative T1DM. Methods: We conducted a multicenter, prospective, observational study of 169 Indian children (age 1-18 years) with recent-onset T1DM. All were tested for antibodies against GAD65, islet antigen-2, and zinc transporter 8 using validated ELISA. Thirty-four islet antibody-negative children underwent targeted next-generation sequencing for 31 genes implicated in monogenic diabetes using the Illumina platform. All mutations were confirmed by Sanger sequencing. Results: Thirty-five (21%) children were negative for all islet antibodies. Twelve patients (7% of entire cohort, 34% of patients with islet antibody-negative T1DM) were detected to have pathogenic or likely pathogenic genetic variants. The most frequently affected locus was WFS1, with 9 patients (5% of entire cohort, 26% of islet antibody-negative). These included 7 children with homozygous and 1 patient each with a compound heterozygous and heterozygous mutation. Children with Wolfram syndrome 1 (WS) presented with severe insulin-requiring diabetes (including 3 patients with ketoacidosis), but other syndromic manifestations were not detected. In 3 patients, heterozygous mutations in HNF4A, ABCC8, and PTF1A loci were detected. Conclusion: Nearly one-quarter of Indian children with islet antibody-negative T1DM had recessive mutations in the WFS1 gene. These patients did not exhibit other features of WS at the time of diagnosis. Testing for monogenic diabetes, especially WS, should be considered in Indian children with antibody-negative T1DM. © 2023 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved.
Novel mutations and spectrum of the disease of NR0B1 (DAX1)-related adrenal insufficiency in Indian children
(De Gruyter, 2019) Suchit Gupta; Kriti Joshi; Ghazala Zaidi; Aditya Narayan Sarangi; Kausik Mandal; Nisha Bhavani; Praveen V. Pavithran; Mini G. Pillai; Surya K. Singh; Tushar Godbole; Vijayalakshmi Bhatia; Eesh Bhatia
X-linked adrenal hypoplasia congenita (AHC), due to mutations in the nuclear receptor superfamily 0, group B, member 1 (NR0B1)/dosage-sensitive sex reversal, AHC, critical region on the X chromosome, gene 1 (DAX1) gene, usually presents with a salt-wasting adrenal crisis in infancy and hypogonadotropic hypogonadism (HH) in adolescents. Genetic reports in the literature from patients of diverse ethnicity are limited. We describe the atypical clinical characteristics and molecular genetic results in six Indian patients. Both exons and flanking intronic sequences of the NR0B1 gene were amplified and sequenced in five patients. In the sixth patient, suspected to have a large deletion, multiplex ligation-dependent probe amplification (MLPA) and chromosomal microarray analysis were performed. Sequencing revealed three novel mutations: A nonsense mutation (c.776C > A), a deletion (c.298del), both causing loss of domains which are highly conserved among nuclear receptor families, and a missense mutation (c.1112T > C). In-silico analysis by structure-based protein modeling predicted a de-stabilizing effect of the novel missense mutation. Two previously reported mutations were seen in patients with atypical manifestations such as late-onset adrenal insufficiency and precocious puberty. One patient had a 7.15-Mb contiguous deletion involving the NR0B1, Duchenne muscular dystrophy (DMD), glycerol kinase (GK) and melanoma antigen, family B, 16 (MAGEB16) genes. Our report emphasizes the wide clinical spectrum of AHC, including rare manifestations, and enumerates unique mutations in the NR0B1 gene. © 2019 Walter de Gruyter GmbH, Berlin/Boston.