Boda Hiroko, Miyata Masafumi, Inagaki Hidehito, Shinkai Yasuko, Kato Takema, Yoshikawa Tetsushi, Kurahashi Hiroki
Department of Pediatrics, Fujita Health University School of Medicine, Japan.
Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Japan; Genome and Transcriptome Analysis Center, Fujita Health University, Japan.
Eur J Med Genet. 2019 Nov;62(11):103570. doi: 10.1016/j.ejmg.2018.11.004. Epub 2018 Nov 8.
We report a patient with congenital complex pituitary hormone deficiency (CPHD) with intestinal malrotation and anal atresia. We identified a de novo heterozygous mutation, c.664T > G (p.Cys222Gly), in the FOXA2 gene in this individual. This missense mutation had the potential to affect the DNA binding properties of the FOXA2 protein based on a protein structure prediction. Since a CPHD patient with another missense mutation and one other case with an entire gene deletion have also been reported, we speculated that a haploinsufficiency of the FOXA2 gene might be a genetic etiology for this disorder. Phenotypic similarities and differences among these three cases are also discussed.
我们报告了一名患有先天性复杂垂体激素缺乏症（CPHD）并伴有肠旋转不良和肛门闭锁的患者。我们在该个体的FOXA2基因中鉴定出一个新发的杂合突变，即c.664T > G（p.Cys222Gly）。基于蛋白质结构预测，这种错义突变有可能影响FOXA2蛋白的DNA结合特性。由于此前也报道过一名患有另一种错义突变的CPHD患者以及另一例整个基因缺失的病例，我们推测FOXA2基因的单倍剂量不足可能是这种疾病的遗传病因。我们还讨论了这三例病例之间的表型异同。
