Bellanné-Chantelot Christine, Chauveau Dominique, Gautier Jean-François, Dubois-Laforgue Danièle, Clauin Séverine, Beaufils Sandrine, Wilhelm Jean-Marie, Boitard Christian, Noël Laure-Hélène, Velho Gilberto, Timsit José
Fédération des Services de Biochimie, Laboratoire de Biologie Moléculaire, Hôpital Saint-Antoine, Paris, France.
Ann Intern Med. 2004 Apr 6;140(7):510-7. doi: 10.7326/0003-4819-140-7-200404060-00009.
Maturity-onset diabetes of the young type 5 (MODY5), a type of dominantly inherited diabetes mellitus and nephropathy, has been associated with mutations of the hepatocyte nuclear factor-1beta (HNF-1beta) gene, mostly generating truncated protein. Various phenotypes, including urogenital malformations, are related to HNF-1beta mutations.
To describe clinical and genetic findings in 13 patients with 8 novel HNF-1beta mutations.
Multicenter, descriptive study.
2 departments of diabetes, 1 department of internal medicine, and 1 department of nephrology.
8 probands with diabetes diagnosed before 40 years of age and nondiabetic kidney disease who were selected independent of their family history of diabetes, and 5 offspring.
Characteristics of diabetes, renal function and structure, genital tract abnormalities, pancreas structure, insulin secretion, exocrine pancreas function, and liver test results.
All mutations, including 5 missense changes, were found in the DNA-binding domain. Cosegregation of the mutation and MODY5 phenotype was observed in 4 families. Occurrence of a de novo mutation was demonstrated in 2 families. Diabetes was present in 10 of 13 mutation carriers. It was clinically overt in 5 participants and found by screening at age 19 to 38 years in 5 participants. Pancreas atrophy was observed in 5 of 6 probands, and pancreas exocrine insufficiency was observed in 6 of 7 probands. Renal involvement, consisting of structural changes and slowly progressive renal failure, was recognized in 9 patients at 18 to 41 years of age. Dysplastic kidneys were found by ultrasonography in 3 fetuses who subsequently showed transient neonatal renal failure. Genital tract abnormalities were present in 5 probands and liver enzyme levels were abnormal in 11 of 13 patients.
Since the study was small and not population-based, it could not estimate the prevalence of MODY5. Other phenotypes might be associated with HNF-1beta mutations.
Maturity-onset diabetes of the young type 5 encompasses a wide clinical spectrum. Analysis for mutations of HNF-1beta is warranted, even without a family history of diabetes, in nonobese patients with diabetes and slowly progressive nondiabetic nephropathy, particularly when pancreatic atrophy or genital abnormalities are present.
青年发病的成年型糖尿病5型（MODY5）是一种常染色体显性遗传的糖尿病及肾病，与肝细胞核因子-1β（HNF-1β）基因突变有关，多数突变产生截短蛋白。包括泌尿生殖系统畸形在内的多种表型与HNF-1β突变相关。
描述13例携带8种新的HNF-1β突变患者的临床及遗传学特征。
多中心描述性研究。
2个糖尿病科、1个内科和1个肾内科。
8例40岁前诊断为糖尿病且患有非糖尿病性肾病的先证者，其选择与糖尿病家族史无关，以及5名后代。
糖尿病特征、肾功能与结构、生殖道异常、胰腺结构、胰岛素分泌、外分泌胰腺功能及肝功能检查结果。
所有突变，包括5个错义改变，均位于DNA结合域。在4个家系中观察到突变与MODY5表型的共分离。在2个家系中证实存在新发突变。13名突变携带者中有10人患有糖尿病。5名参与者临床糖尿病表现明显，5名参与者在19至38岁筛查时发现糖尿病。6例先证者中有5例观察到胰腺萎缩，7例先证者中有6例观察到胰腺外分泌功能不全。9例18至41岁患者存在肾脏受累，包括结构改变和缓慢进展的肾衰竭。3例胎儿超声检查发现肾发育异常，随后出现短暂性新生儿肾衰竭。5例先证者存在生殖道异常，13例患者中有11例肝功能酶水平异常。
由于本研究规模小且非基于人群，无法估计MODY5的患病率。其他表型可能与HNF-1β突变相关。
青年发病的成年型糖尿病5型临床谱广泛。对于非肥胖的糖尿病患者及缓慢进展的非糖尿病性肾病患者，即使无糖尿病家族史，尤其是存在胰腺萎缩或生殖器异常时，进行HNF-1β突变分析是必要的。
