Serviço de Genética Médica, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
Escola de Medicina da Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
Am J Med Genet A. 2024 Dec;194(12):e63836. doi: 10.1002/ajmg.a.63836. Epub 2024 Aug 16.
Holoprosencephaly (HPE) results from a lack of cleavage of the prosencephalon. It has a complex etiology, resulting from chromosome abnormalities or single gene variants in the Sonic hedgehog signaling pathway. A single variant, p.Arg535Cys in CNOT1, has been described in HPE in association with pancreatic agenesis and neonatal diabetes. Here, we report on a case of HPE and p.Arg535Cys in CNOT1 without pancreatic agenesis where the patient presented with diabetes mellitus in adolescence. This case reinforces the role of CNOT1 in pancreatic development. We suggest that individuals with p.Arg535Cys in CNOT1 with no pancreas abnormalities observed at birth should be screened for diabetes during follow-up.
前脑无裂畸形（HPE）是由于前脑未能分裂所致。它的病因复杂，是由染色体异常或 Sonic hedgehog 信号通路中的单个基因突变引起的。在与胰腺发育不全和新生儿糖尿病相关的 HPE 中，已经描述了 CNOT1 中的单个变体 p.Arg535Cys。在这里，我们报告了一例 HPE 和 CNOT1 中的 p.Arg535Cys 病例，患者在青春期时表现出糖尿病。该病例进一步证实了 CNOT1 在胰腺发育中的作用。我们建议，出生时无胰腺异常但存在 CNOT1 p.Arg535Cys 的个体应在随访期间接受糖尿病筛查。
