title: Comprehensive Maturity Onset Diabetes of the Young (MODY) Gene Screening in Pregnant Women with Diabetes in India.
abstract: Pregnant women with diabetes may have underlying beta cell dysfunction due to mutations/rare variants in genes associated with Maturity Onset Diabetes of the Young (MODY). MODY gene screening would reveal those women genetically predisposed and previously unrecognized with a monogenic form of diabetes for further clinical management, family screening and genetic counselling. However, there are minimal data available on MODY gene variants in pregnant women with diabetes from India. In this study, utilizing the Next generation sequencing (NGS) based protocol fifty subjects were screened for variants in a panel of thirteen MODY genes. Of these subjects 18% (9/50) were positive for definite or likely pathogenic or uncertain MODY variants. The majority of these variants was identified in subjects with autosomal dominant family history, of whom five were in women with pre-GDM and four with overt-GDM. The identified variants included one patient with HNF1A Ser3Cys, two PDX1 Glu224Lys, His94Gln, two NEUROD1 Glu59Gln, Phe318Ser, one INS Gly44Arg, one GCK, one ABCC8 Arg620Cys and one BLK Val418Met variants. In addition, three of the seven offspring screened were positive for the identified variant. These identified variants were further confirmed by Sanger sequencing. In conclusion, these findings in pregnant women with diabetes, imply that a proportion of GDM patients with autosomal dominant family history may have MODY. Further NGS based comprehensive studies with larger samples are required to confirm these finding.
authors.affiliation: Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, India.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Doddabelavangala Mruthyunjaya
authors.affiliation: Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, India.
authors.forename: Aaron
authors.initials: A
authors.lastname: Chapla
authors.affiliation: Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, India.
authors.forename: Asha
authors.initials: A
authors.lastname: Hesarghatta Shyamasunder
authors.affiliation: Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, India.
authors.forename: Deny
authors.initials: D
authors.lastname: Varghese
authors.affiliation: Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, India.
authors.forename: Manika
authors.initials: M
authors.lastname: Varshney
authors.affiliation: Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, India.
authors.forename: Johan
authors.initials: J
authors.lastname: Paul
authors.affiliation: Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, India.
authors.forename: Mercy
authors.initials: M
authors.lastname: Inbakumari
authors.affiliation: Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, India.
authors.forename: Flory
authors.initials: F
authors.lastname: Christina
authors.affiliation: Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, India.
authors.forename: Ron Thomas
authors.initials: RT
authors.lastname: Varghese
authors.affiliation: Department of Neonatology, Christian Medical College, Vellore, India.
authors.forename: Kurien Anil
authors.initials: KA
authors.lastname: Kuruvilla
authors.affiliation: Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, India.
authors.forename: Thomas
authors.initials: T
authors.lastname: V Paul
authors.affiliation: Department of Obstetrics and Gynaecology, Christian Medical College, Vellore, India.
authors.forename: Ruby
authors.initials: R
authors.lastname: Jose
authors.affiliation: Department of Obstetrics and Gynaecology, Christian Medical College, Vellore, India.
authors.forename: Annie
authors.initials: A
authors.lastname: Regi
authors.affiliation: Department of Obstetrics and Gynaecology, Christian Medical College, Vellore, India.
authors.forename: Jessie
authors.initials: J
authors.lastname: Lionel
authors.affiliation: Department of Biostatistics, Christian Medical College, Vellore, India.
authors.forename: L
authors.initials: L
authors.lastname: Jeyaseelan
authors.affiliation: Department of Obstetrics and Gynaecology, Christian Medical College, Vellore, India.
authors.forename: Jiji
authors.initials: J
authors.lastname: Mathew
authors.affiliation: Department of Endocrinology, Diabetes & Metabolism, Christian Medical College, Vellore, India.
authors.forename: Nihal
authors.initials: N
authors.lastname: Thomas
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011247:Pregnancy
chemical_list: D015415:Biomarkers