An Indian child with Coats plus syndrome due to mutations in STN1.

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.

• Authors: Gouri Rao Passi, Uzma Shamim, Surabhi Rathore, Aditi Joshi, Aradhana Mathur, Shaista Parveen, Pooja Sharma, Yanick J Crow, Mohammed Faruq
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 182 Issue 9 Pg. 2139-2144 (09 2020) ISSN: 1552-4833 [Electronic] United States
• PMID: 32627942 (Publication Type: Case Reports)
• Copyright: © 2020 Wiley Periodicals LLC.

Chemical References

• Stn1 protein, human
• Telomere-Binding Proteins
• Ten1 protein, human

Topics

• Asian People (genetics)
• Ataxia (genetics, pathology)
• Brain Neoplasms (genetics, pathology)
• Calcinosis (genetics, pathology)
• Central Nervous System Cysts (genetics, pathology)
• DNA Replication (genetics)
• Female
• Humans
• Infant
• Leukoencephalopathies (genetics, pathology)
• Muscle Spasticity (genetics, pathology)
• Mutation (genetics)
• Phenotype
• Retinal Diseases (genetics, pathology)
• Seizures (genetics, pathology)
• Telomere (genetics)
• Telomere Homeostasis (genetics)
• Telomere-Binding Proteins (genetics)