An Indian child with Coats plus syndrome due to mutations in STN1. Issue 9 (6th July 2020)

• Record Type: Journal Article
• Authors: Passi, Gouri Rao; Shamim, Uzma; Rathore, Surabhi; Joshi, Aditi; Mathur, Aradhana; Parveen, Shaista; Sharma, Pooja; Crow, Yanick J.; Faruq, Mohammed
• Is Part Of: American journal of medical genetics. Volume 182:Issue 9(2020)
• Page Start: 2139
• Page End: 2144
• Publication Date: 2020-07-06
• Subjects: coats plus -- hormonal therapy -- STN1; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.61737
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract: 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.