The role of the CTC1–STN1–TEN1 (CST) complex in Coats plus syndrome (CP), as well as other telomeropathy‐phenotypes and disorders of genome instability is well documented. We report an Indian child with a clinical diagnosis of CP who presented to us with retinal exudates, extensive cerebral calcification, developmental delay and severe anemia consequent upon chronic gastrointestinal (GI) bleeding. Whole exome sequencing revealed compound heterozygous variants in STN1 as the probable genetic cause leading to CP in the present case. Of the two variants, the nonsense variant c.397C>T (p.Arg133*) was a truncating variant leading to loss of full protein length whereas the second variant c.985G>C (p.Ala329Pro) was novel and neither reported in ExAC, 1KGP or gnomAD. The deleteriousness of the novel variant was explored through molecular dynamics simulation analysis where p.Ala329Pro mutation affected C‐terminal domain interaction between STN1 and TEN1 complex. Hormonal therapy using ethinyl estradiol and norethisterone was apparently associated with a clinically useful, although poorly sustained, decrease in blood transfusion requirement in the proband.

中文翻译：

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一名因STN1突变而患有大衣加综合征的印度儿童。

CTC1-STN1-TEN1（CST）复合体在高士加症候群（CP）以及其他端粒病表型和基因组不稳定疾病中的作用已得到充分证明。我们报告了一名患有CP的临床诊断的印度儿童，该儿童因慢性胃肠道（GI）出血而出现视网膜渗出液，广泛的脑钙化，发育迟缓和严重贫血。整个外显子组测序揭示了STN1中的化合物杂合变异体在本案中可能是导致CP的遗传原因。在这两个变体中，无意义的变体c.397C> T（p.Arg133 *）是截短的变体，导致蛋白质全长损失，而第二个变体c.985G> C（p.Ala329Pro）是新颖的，均未见报道。 ExAC，1KGP或gnomAD。通过分子动力学模拟分析探索了该新变异体的有害性，其中p.Ala329Pro突变影响STN1和TEN1复合体之间的C末端结构域相互作用。使用炔雌醇和炔诺酮进行激素治疗显然与临床有用，尽管持续时间较差，但先证者的输血需求减少。