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Abstract：
ALG12-congenital disorder of glycosylation (ALG12-CDG) is a rare disorder caused by a deficiency of dolichol-P-mannose:Man7GlcNAc2-PP-dolichyl-α-6-mannosyltransferase which presents with intellectual disability, hypotonia, dysmorphic features, low IgG levels with recurrent infections, male genital hypoplasia, and coagulation abnormalities. We report a unique family with three affected individuals, including two older brothers with only cognitive and coagulation defects and a younger brother who died from a severe multisystem disease at age 18 months. The two living brothers are the oldest and mildest cases of ALG12-CDG described thus far. Whole exome sequencing of the older brothers revealed a previously described c.1001delA (p.N334TfsX15) pathogenic variant and a c.671C > T (p.T224 M) variant of uncertain significance in ALG12. Our cases broaden the recognized genetic and phenotypic spectrum of this disorder and suggest a role for other genetic and environmental factors in modulating disease phenotype.
摘要：
ALG12-先天性糖基化障碍（ALG12-CDG）是一种罕见的疾病，由多力胆碱-P-甘露糖缺乏引起：Man7GlcNAc2-PP-dolichyl-α-6-甘露糖基转移酶表现为智力障碍，低张力,变形特征，低IgG水平与复发性感染，男性生殖器发育不全,和凝血异常。我们报告了一个独特的家庭，有三个受影响的人，包括两个只有认知和凝血缺陷的哥哥和一个在18个月大时死于严重多系统疾病的弟弟。这两个活着的兄弟是迄今为止描述的最古老，最温和的ALG12-CDG病例。哥哥们的整个外显子组测序揭示了先前描述的c.1001delA（p。N334TfsX15）致病性变体和c.671C>T（p。T224M）在ALG12中具有不确定意义的变体。我们的病例拓宽了该疾病的公认遗传和表型谱，并暗示了其他遗传和环境因素在调节疾病表型中的作用。
