COG6‐congenital disorder of glycosylation (COG6‐CDG) is caused by biallelic mutations in COG6. To‐date, 12 variants causing COG6‐CDG in less than 20 patients have been reported. Using whole exome sequencing we identified two siblings with a novel homozygous deletion of 26 bp in COG6, creating a splicing variant (c.518_540 + 3del) and a shift in the reading frame. The phenotype of COG6‐CDG includes growth and developmental retardation, microcephaly, liver and gastrointestinal disease, hypohydrosis and recurrent infections. We report two patients with novel phenotypic features including bowel malrotation and ambiguous genitalia, directing attention to the role of glycoprotein metabolism in the causation of disorders of sex development (DSD). Searching the glycomic literature, we identified 14 CDGs including males with DSD, a feature not previously accentuated. This study broadens the genetic and phenotypic spectrum of COG6‐CDG and calls for increasing awareness to the central role of glycosylation processes in development of human sex and genitalia.

中文翻译：

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COG6-CDG：扩大表型，重点是男性性别发育障碍的糖基化缺陷。

COG6先天性糖基化疾病（COG6-CDG）是由COG 6中的双等位基因突变引起的。迄今为止，已报道了不足20名患者的12种引起COG6-CDG的变异。使用整个外显子组测序，我们确定了两个同胞，它们在COG6中有一个新的纯合子缺失26 bp，创建一个拼接变体（c.518_540 + 3del），并在阅读框中进行移位。COG6-CDG的表型包括生长发育迟缓，小头畸形，肝脏和胃肠道疾病，脱水不足和反复感染。我们报道了两名患者的新型表型特征，包括肠蠕动和生殖器模棱两可，从而引起人们对糖蛋白代谢在性发育障碍（DSD）病因中的作用的关注。通过搜索糖类文献，我们发现了14种CDG，包括DSD男性，这一特征以前并未被强调。这项研究拓宽了COG6-CDG的遗传和表型谱，并呼吁人们提高对糖基化过程在人类性别和生殖器发育中的核心作用的认识。