Du Yang Timothy, Moore Lynette, Poplawski Nicola K, De Sousa Sunita M C
Endocrine and Metabolic Unit, Royal Adelaide Hospital.
School of Medicine, University of Adelaide.
Endocrinol Diabetes Metab Case Rep. 2019 May 3;2019. doi: 10.1530/EDM-19-0022.
A 26-year-old man presented with a combination of permanent neonatal diabetes due to pancreatic aplasia, complex congenital heart disease, central hypogonadism and growth hormone deficiency, structural renal abnormalities with proteinuria, umbilical hernia, neurocognitive impairment and dysmorphic features. His older brother had diabetes mellitus due to pancreatic hypoplasia, complex congenital heart disease, hypospadias and umbilical hernia. Their father had an atrial septal defect, umbilical hernia and diabetes mellitus diagnosed incidentally in adulthood on employment screening. The proband's paternal grandmother had a congenital heart defect. Genetic testing of the proband revealed a novel heterozygous missense variant (Chr18:g.19761441T>C, c.1330T>C, p.Cys444Arg) in exon 4 of GATA6, which is class 5 (pathogenic) using American College of Medical Genetics and Genomics guidelines and is likely to account for his multisystem disorder. The same variant was detected in his brother and father, but not his paternal grandmother. This novel variant of GATA6 likely occurred de novo in the father with autosomal dominant inheritance in the proband and his brother. The case is exceptional as very few families with monogenic diabetes due to GATA6 mutations have been reported to date and we describe a new link between GATA6 and renal pathology. Learning points: Monogenic diabetes should be suspected in patients presenting with syndromic features, multisystem congenital disease, neonatal-onset diabetes and/or a suggestive family history. Recognition and identification of genetic diabetes may improve patient understanding and empowerment and allow for better tailored management. Identification of a genetic disorder may have important implications for family planning.
一名26岁男性患者，患有因胰腺发育不全导致的永久性新生儿糖尿病、复杂先天性心脏病、中枢性性腺功能减退和生长激素缺乏、伴有蛋白尿的结构性肾脏异常、脐疝、神经认知障碍和畸形特征。他的哥哥患有因胰腺发育不全、复杂先天性心脏病、尿道下裂和脐疝导致的糖尿病。他们的父亲有房间隔缺损、脐疝，在成年就业筛查时偶然诊断出患有糖尿病。先证者的祖母有先天性心脏缺陷。对先证者进行基因检测发现，GATA6基因第4外显子有一个新的杂合错义变异（Chr18:g.19761441T>C，c.1330T>C，p.Cys444Arg），根据美国医学遗传学与基因组学学会的指南，该变异属于5类（致病性），可能是导致他多系统疾病的原因。在他的哥哥和父亲中也检测到了相同的变异，但他的祖母没有。GATA6基因的这个新变异可能是在父亲中新生发生的，在先证者及其哥哥中呈常染色体显性遗传。该病例很罕见，因为迄今为止报道的因GATA6突变导致单基因糖尿病的家庭很少，并且我们描述了GATA6与肾脏病理之间的新联系。学习要点：对于出现综合征特征、多系统先天性疾病、新生儿期糖尿病和/或提示性家族史的患者，应怀疑单基因糖尿病。识别和鉴定遗传性糖尿病可能会提高患者的理解和自主权，并有助于进行更有针对性的管理。识别遗传疾病可能对计划生育具有重要意义。
