GATA6 mutations cause a broad phenotypic spectrum of diabetes from pancreatic agenesis to adult-onset diabetes without exocrine insufficiency.
GATA6 mutations cause a broad phenotypic spectrum of diabetes from pancreatic agenesis to adult-onset diabetes without exocrine insufficiency.
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作者：
De Franco E;Shaw-Smith C;Flanagan SE;Shepherd MH;International NDM Consortium;Hattersley AT;Ellard S
我们最近报道了新生GATA 6突变是胰腺发育不全的最常见原因，占27例胰岛素治疗的新生儿糖尿病和需要酶替代治疗的胰腺外分泌功能不全患者中的15例（56%）。我们研究了GATA 6突变在795例新生儿糖尿病患者队列中171例遗传病因不明的新生儿糖尿病患者中的作用。在624例患者中证实了已知基因的突变（包括15个GATA 6突变）。其余171例患者的测序确定了9例新病例受试者（795例中的24例，3%）。胰腺发育不全存在于21例受试者（6例新）; 2例患者有永久性新生儿糖尿病，无酶补充，1例有短暂性新生儿糖尿病。4名GATA 6杂合突变的父母在新生儿期（12-46岁）外被诊断为糖尿病。亚临床外分泌功能不全，表现为低粪便弹性蛋白酶在四个糖尿病患者谁没有收到酶补充。其中一个有嵌合突变的父母没有糖尿病，但有心脏畸形。在所有24名先证者和3名父母中观察到胰腺外特征，其中先天性心脏病最常见（83%）。杂合GATA 6突变引起广泛的糖尿病表现，从胰腺发育不全到伴有亚临床或无外分泌功能不全的成人型糖尿病。
We recently reported de novo GATA6 mutations as the most common cause of pancreatic agenesis, accounting for 15 of 27 (56%) patients with insulin-treated neonatal diabetes and exocrine pancreatic insufficiency requiring enzyme replacement therapy. We investigated the role of GATA6 mutations in 171 subjects with neonatal diabetes of unknown genetic etiology from a cohort of 795 patients with neonatal diabetes. Mutations in known genes had been confirmed in 624 patients (including 15 GATA6 mutations). Sequencing of the remaining 171 patients identified nine new case subjects (24 of 795, 3%). Pancreatic agenesis was present in 21 case subjects (six new); two patients had permanent neonatal diabetes with no enzyme supplementation and one had transient neonatal diabetes. Four parents with heterozygous GATA6 mutations were diagnosed with diabetes outside the neonatal period (12–46 years). Subclinical exocrine insufficiency was demonstrated by low fecal elastase in three of four diabetic patients who did not receive enzyme supplementation. One parent with a mosaic mutation was not diabetic but had a heart malformation. Extrapancreatic features were observed in all 24 probands and three parents, with congenital heart defects most frequent (83%). Heterozygous GATA6 mutations cause a wide spectrum of diabetes manifestations, ranging from pancreatic agenesis to adult-onset diabetes with subclinical or no exocrine insufficiency.
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