葡萄牙一个大型队列中的青年成年型糖尿病

Maturity-onset diabetes of the young in a large Portuguese cohort.

作者信息

Santos Monteiro Sílvia, da Silva Santos Tiago, Fonseca Liliana, Assunção Guilherme, Lopes Ana M, Duarte Diana B, Soares Ana Rita, Laranjeira Francisco, Ribeiro Isaura, Pinto Eugénia, Rocha Sónia, Barbosa Gouveia Sofia, Vazquez-Mosquera María Eugenia, Oliveira Maria João, Borges Teresa, Cardoso Maria Helena

机构信息

Division of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário do Porto, Largo Professor Abel Salazar, 4099-001, Porto, Portugal.

Division of Medical Genetics, Centro de Genética Médica Doutor Jacinto Magalhães, Centro Hospitalar Universitário do Porto, Porto, Portugal.

出版信息

Acta Diabetol. 2023 Jan;60(1):83-91. doi: 10.1007/s00592-022-01980-2. Epub 2022 Oct 8.

DOI:10.1007/s00592-022-01980-2

PMID:36208343

Abstract

AIMS

Monogenic forms of diabetes that develop with autosomal dominant inheritance are classically aggregated in the Maturity-Onset Diabetes of the Young (MODY) categories. Despite increasing awareness, its true prevalence remains largely underestimated. We describe a Portuguese cohort of individuals with suspected monogenic diabetes who were genetically evaluated for MODY-causing genes.

METHODS

This single-center retrospective cohort study enrolled patients with positive genetic testing for MODY between 2015 and 2021. Automatic sequencing and, in case of initial negative results, next-generation sequencing were performed. Their clinical and molecular characteristics were described.

RESULTS

Eighty individuals were included, 55 with likely pathogenic/pathogenic variants in one of the MODY genes and 25 MODY-positive family members, identified by cascade genetic testing. The median age at diabetes diagnosis was 23 years, with a median HbA1c of 6.5%. The most frequently mutated genes were identified in HNF1A (40%), GCK (34%) and HNF4A (13%), followed by PDX1, HNF1B, INS, KCNJ11 and APPL1. Thirty-six unique variants were found (29 missense and 7 frameshift variants), of which ten (28%) were novel.

CONCLUSIONS

Our data highlights the importance of genetic testing in the diagnosis of MODY and the establishment of its subtypes, leading to more personalized treatment and follow-up strategies.

摘要

目的

以常染色体显性遗传方式发病的单基因糖尿病经典地聚集在青少年成年起病型糖尿病（MODY）类别中。尽管人们的认识不断提高，但其真实患病率仍在很大程度上被低估。我们描述了一组葡萄牙疑似单基因糖尿病个体，他们接受了针对MODY致病基因的基因评估。

方法

这项单中心回顾性队列研究纳入了2015年至2021年间MODY基因检测呈阳性的患者。进行了自动测序，若初始结果为阴性，则进行二代测序。描述了他们的临床和分子特征。

结果

共纳入80人，其中55人在一个MODY基因中存在可能致病/致病的变异，25名MODY阳性家庭成员通过级联基因检测确定。糖尿病诊断时的中位年龄为23岁，HbA1c中位数为6.5%。最常发生突变的基因是HNF1A（40%）、GCK（34%）和HNF4A（13%），其次是PDX1、HNF1B、INS、KCNJ11和APPL1。共发现36种独特变异（29种错义变异和7种移码变异），其中10种（28%）是新发现的。