Max Delbrück Center for Molecular Medicine, Charité, Berlin, Germany.
Horm Res Paediatr. 2013;79(4):250-6. doi: 10.1159/000348844. Epub 2013 Apr 26.
GATA6 mutations are the most frequent cause of pancreatic agenesis and diabetes in human sporadic cases. In families, dominantly inherited mutations show a variable phenotype also in terms of endocrine and exocrine pancreatic disease. We report two novel GATA6 mutations in an independent cohort of 8 children with pancreas aplasia or hypoplasia and diabetes.
We sequenced GATA6 in 8 children with diabetes and inborn pancreas abnormalities, i.e. hypoplasia or aplasia in which other known candidate genes causing monogenic diabetes and pancreatic defects had been excluded.
We found two novel heterozygous GATA6 mutations (c.951_954dup and c.754_904del) in 2 patients with sporadic pancreas hypoplasia, diabetes and severe cardiac defects (common truncus arteriosus and tetralogy of Fallot), but not in the remaining 6 patients. GATA6 mutations in carriers exhibited hypoplastic pancreas with absent head in 1 patient and with increased echogenicity and decreasing exocrine function in the other patient. Additionally, hepatobiliary malformations and brain atrophy were found in 1 patient.
Our 2 cases with novel GATA6 mutations add more phenotype characteristics of GATA6 haploinsufficiency. In agreement with an increasing number of published cases, the wide phenotypic spectrum of GATA6 diabetes syndrome should draw the attention of both pediatric endocrinologists and geneticists.
GATA6 突变是人类散发性病例中胰腺发育不全和糖尿病的最常见原因。在家族中，显性遗传突变也表现出内分泌和外分泌胰腺疾病的可变表型。我们报道了 8 例胰腺发育不全或发育不良伴糖尿病的独立队列中 2 个新的 GATA6 突变。
我们对 8 例糖尿病和先天性胰腺异常（即发育不全或发育不全）的儿童进行了 GATA6 测序，这些儿童排除了其他已知导致单基因糖尿病和胰腺缺陷的候选基因。
我们在 2 例散发性胰腺发育不全、糖尿病和严重心脏缺陷（共同动脉干和法洛四联症）的患者中发现了 2 个新的杂合 GATA6 突变（c.951_954dup 和 c.754_904del），但在其余 6 例患者中未发现。携带者的 GATA6 突变在 1 例患者中表现为胰腺发育不全，头部缺失，另 1 例患者表现为回声增强和外分泌功能下降。此外，1 例患者还发现了肝胆畸形和脑萎缩。
我们的 2 例新的 GATA6 突变病例增加了 GATA6 单倍体不足的更多表型特征。与越来越多的已发表病例一致，GATA6 糖尿病综合征的广泛表型谱应引起儿科内分泌学家和遗传学家的关注。
