Targeted sequencing identifies novel variants in common and rare MODY genes

Autor(es):Mostrar menos -

de Santana, Lucas S. ^{[1, 2]} ; Caetano, Lilian A. ^{[1, 2, 3]} ; Costa-Riquetto, Aline D. ^{[1, 2, 3]} ; Franco, Pedro C. ^{[1, 2, 3]} ; Dotto, Renata P. ^[4] ; Reis, Andre F. ^[4] ; Weinert, Leticia S. ^[5] ; Silveiro, Sandra P. ^[5] ; Vendramini, Marcio F. ^[6] ; do Prado, Flaviene A. ^[7] ; Abrahao, Giovanna C. P. ^[8] ; de Almeida, Ana Gregoria F. P. ^[9] ; Rodrigues Tavares, Maria da G. ^[10] ; Goncalves, Wagner Rodrigo B. ^[11] ; Santomauro Junior, Augusto C. ^[12] ; Halpern, Bruno ^[13] ; Jorge, Alexander A. L. ^{[1, 2]} ; Nery, Marcia ^[3] ; Teles, Milena G. ^{[1, 2, 3]}

Afiliação do(s) autor(es):Mostrar menos -

^[1] Univ Sao Paulo, Sch Med, Monogen Diabet Grp, Genet Endocrinol Unit, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Sch Med, Lab Mol & Cellular Endocrinol LIM25, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Sch Med, Clin Hosp, Diabet Unit, Sao Paulo, SP - Brazil

^[4] Univ Fed Sao Paulo UNIFESP, Dept Med, Disciplina Endocrinol, Sao Paulo, SP - Brazil

^[5] Univ Fed Rio Grande do Sul, Porto Alegre, RS - Brazil

^[6] HSPE SP, Serv Endocrinol, Sao Paulo, SP - Brazil

^[7] Hosp Reg Taguatinga Secretaria Saude Dist Fed, Taguatinga, DF - Brazil

^[8] PUCSP, Sao Paulo, SP - Brazil

^[9] Inst Fed Educ Ciencia & Tecnol Maranhao IFMA, Sao Luis, Maranhao - Brazil

^[10] Univ Fed Maranhao UFMA, Serv Endocrinol, Hosp Univ, Sao Luis, Maranhao - Brazil

^[11] HSPM SP, Sao Paulo, SP - Brazil

^[12] Hosp Beneficencia Portuguesa Sao Paulo BP SP, Serv Endocrinol Prof Dr Fadlo Fraige Filho, Sao Paulo, SP - Brazil

^[13] Univ Sao Paulo, Fac Med, Hosp Clin, Dept Endocrinol & Metab, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: MOLECULAR GENETICS & GENOMIC MEDICINE; v. 7, n. 12 DEC 2019.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 17/14703-4 - Estudo do exoma em famílias com diagnóstico clínico de MODY (Maturity-Onset Diabetes of the Young) e Diabetes Mellitus Neonatal
• Beneficiário: Lucas Santos de Santana
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/19920-2 - Estudo genético-molecular por sequenciamento de nova geração de pacientes com diagnóstico clínico de MODY (Maturity onset diabetes of the Young)
• Beneficiário: Milena Gurgel Teles Bezerra
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/15365-5 - ESTUDO DO EXOMA EM FAMÍLIAS COM DIAGNÓSTICO CLÍNICO DE MODY (Maturity-Onset Diabetes of the Young) E DIABETES MELLITUS NEONATAL
• Beneficiário: Milena Gurgel Teles Bezerra
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/05123-9 - Estratificação de risco de doença cardiovascular em pacientes com Diabetes mellitus monogênico tipo MODY
• Beneficiário: André Fernandes Reis
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/02162-8 - Patogênese molecular e caracterização de doenças monogênicas do desenvolvimento: um caminho para a medicina translacional
• Beneficiário: Berenice Bilharinho de Mendonça
• Modalidade de apoio: Auxílio à Pesquisa - Temático