Open AccessTargeted sequencing identifies novel variants in common and rare MODY genes
Author(s) -
Santana Lucas S.,
Caetano Lilian A.,
CostaRiquetto Aline D.,
Franco Pedro C.,
Dotto Renata P.,
Reis André F.,
Weinert Letícia S.,
Silveiro Sandra P.,
Vendramini Marcio F.,
Prado Flaviene A.,
Abrahão Giovanna C. P.,
Almeida Ana Gregória F. P.,
Tavares Maria da G. Rodrigues,
Gonçalves Wagner Rodrigo B.,
Santomauro Junior Augusto C.,
Halpern Bruno,
Jorge Alexander A. L.,
Nery Marcia,
Teles Milena G.
Publication year - 2019
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.962
Subject(s) - hnf1a , proband , hnf1b , maturity onset diabetes of the young , medicine , genetic testing , genetic heterogeneity , genetics , phenotype , mutation , gene , bioinformatics , biology , gene expression , homeobox
Background Maturity‐onset diabetes of the young (MODY) is a form of monogenic diabetes with autosomal dominant inheritance. To date, mutations in 11 genes have been frequently associated with this phenotype. In Brazil, few cohorts have been screened for MODY, all using a candidate gene approach, with a high prevalence of undiagnosed cases (MODY‐X). Methods We conducted a next‐generation sequencing target panel (tNGS) study to investigate, for the first time, a Brazilian cohort of MODY patients with a negative prior genetic analysis. One hundred and two patients were selected, of which 26 had an initial clinical suspicion of MODY‐ GCK and 76 were non‐ GCK MODY. Results After excluding all benign and likely benign variants and variants of uncertain significance, we were able to assign a genetic cause for 12.7% (13/102) of the probands. Three rare MODY subtypes were identified ( PDX1 / NEUROD1 / ABCC8 ), and eight variants had not been previously described/mapped in genomic databases. Important clinical findings were evidenced in some cases after genetic diagnosis, such as MODY‐ PDX1 / HNF1B . Conclusion A multiloci genetic approach allowed the identification of rare MODY subtypes, reducing the large percentage of MODY‐X in Brazilian cases and contributing to a better clinical, therapeutic, and prognostic characterization of these rare phenotypes.