PDX1-MODY and dorsal pancreatic agenesis: New phenotype of a rare disease

Autor(es)

Caetano, L. A. ^{[1, 2]} ; Santana, L. S. ^[2] ; Costa-Riquetto, A. D. ^{[1, 2]} ; Lerario, A. M. ^{[3, 2]} ; Nery, M. ^[1] ; Nogueira, G. F. ^[4] ; Ortega, C. D. ^[4] ; Rocha, M. S. ^[5] ; Jorge, A. A. L. ^[2] ; Teles, M. G. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Med, Clin Hosp, Diabet Unit, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, LIM25, Genet Endocrinol Unit, Monogen Diabet Grp, Sao Paulo - Brazil

^[3] Univ Michigan, Dept Internal Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 - USA

^[4] Univ Sao Paulo, Sch Med, Clin Hosp, Inst Radiol, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Sch Med, Dept Radiol & Oncol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Clinical Genetics; v. 93, n. 2, p. 382-386, FEB 2018.
• Citações Web of Science: 3

Resumo

Maturity-Onset Diabetes of the Young (MODY) type 4 or PDX1-MODY is a rare form of monogenic diabetes caused by heterozygous variants in PDX1. Pancreatic developmental anomalies related to PDX1 are reported only in neonatal diabetes cases. Here, we describe dorsal pancreatic agenesis in 2 patients with PDX1-MODY. The proband presented with diabetes since 14 years of age and maintained regular glycemic control with low doses of basal insulin and detectable C-peptide levels after 38 years with diabetes. A diagnosis of MODY was suspected. Targeted next-generation sequencing identified a heterozygous variant in PDX1: c.188delC/p. Pro63Argfs{*}60. Computed tomography revealed caudal pancreatic agenesis. Low fecal elastase indicated exocrine insufficiency. His son had impaired glucose tolerance, presented similar pancreatic agenesis, and harbored the same allelic variant. The unusual presentation in this Brazilian family enabled expansion upon a rare disease phenotype, demonstrating the possibility of detecting pancreatic malformation even in cases of PDX1-related diabetes diagnosed after the first year of life. This finding can improve the management of MODY4 patients, leading to precocious investigation of pancreatic dysgenesis and exocrine dysfunction. (AU)

• 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
• 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