Phenotypic Heterogeneity in a Congenital Disorder of Glycosylation Caused by Mutations in STT3A
Phenotypic Heterogeneity in a Congenital Disorder of Glycosylation Caused by Mutations in STT3A
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DOI：
10.1177/0883073817696816
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发表时间：
2017-05-01
影响因子：
1.9
通讯作者：
Clayton-Smith, Jill
中科院分区：
文献类型：
--
作者：
Ghosh, Arunabha;Urquhart, Jill;Clayton-Smith, Jill
STT3A编码寡糖基转移酶复合物的催化亚基。迄今为止，仅在一个家族中报道过由STT3A突变引起的先天性糖基化障碍，其与转铁蛋白糖型的I型先天性糖基化障碍模式相关。作者描述了另外5名相关个体，他们在STT3A中可能存在致病变异，其中2人在TUSC3中也存在变异。所有有症状个体的常见表型特征包括发育迟缓、智力残疾、语言缺失和癫痫发作。两名个体还出现了发作性低体温和意识改变。通过纯合子定位对该家族进行了研究，结果显示一个孩子既存在包含STT3A的纯合区域，此外还存在TUSC3的纯合缺失。通过对所有受影响个体进行桑格测序，确认了STT3A中一个可能的致病变异：作者详细讨论了分子研究结果，并进一步描绘了这种罕见疾病的临床表型。
STT3A encodes the catalytic subunit of the oligosaccharyltransferase complex. A congenital disorder of glycosylation caused by mutations in STT3A has only been reported in one family to date, associated with a Type I congenital disorder of glycosylation pattern of transferrin glycoforms. The authors describe a further 5 related individuals with a likely pathogenic variant in STT3A, 2 of whom also had variants in TUSC3. Common phenotypic features in all symptomatic individuals include developmental delay, intellectual disability, with absent speech and seizures. Two individuals also developed episodic hypothermia and altered consciousness. The family were investigated by autozygosity mapping, which revealed both a homozygous region containing STT3A and, in addition, a homozygous deletion of TUSC3 in one child. A likely pathogenic variant in STT3A was confirmed on Sanger sequencing of all affected individuals: the authors discuss the molecular findings in detail and further delineate the clinical phenotype of this rare disorder.