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Novel compound heterozygous STN1 variants are associated with Coats Plus syndrome
- Source :
- Acharya, T, Firth, H, Dugar, S, Grammatikopoulos, T, Seabra, L, Walters, A, Crow, Y J & Parker, A PJ 2021, ' Novel compound heterozygous STN1 variants are associated with Coats Plus syndrome ', Molecular Genetics and Genomic Medicine . https://doi.org/10.1002/mgg3.1708, Molecular Genetics & Genomic Medicine, Vol 9, Iss 12, Pp n/a-n/a (2021), Molecular Genetics & Genomic Medicine
- Publication Year :
- 2021
-
Abstract
- Funder: Wellcome<br />Aim: Coats plus syndrome (CP) is a rare autosomal recessive disorder, characterised by retinal telangiectasia exudates (Coats disease), leukodystrophy, distinctive intracranial calcification and cysts, as well as extra‐neurological features including abnormal vasculature of the gastrointestinal tract, portal hypertension and osteopenia with a tendency to fractures. CP most frequently occurs due to loss‐of‐function mutations in CTC1. The encoded protein CTC1 constitutes part of the CST (CTC1‐STN1‐TEN1) complex, and three patients have been described with CP due to biallelic mutations in STN1. Together with the identification of homozygosity for a specific loss‐of‐function mutation in POT1 in a sibling pair, these observations highlight a defect in the maintenance of telomere integrity as the cause of CP, although the precise mechanism leading to the micro‐vasculopathy seen at a pathological level remains unclear. Here, we present the investigation of a fourth child who presented to us with retinal exudates, intracranial calcifications and developmental delay, in keeping with a diagnosis of CP, and later went on to develop pancytopenia and gastrointestinal bleeding. Genome sequencing revealed compound heterozygous variants in STN1 as the likely genetic cause of CP in this present case. Methods: We assessed the phenotype to be CP and undertook targeted sequencing. Results: Whilst sequencing of CTC1 and POT1 was normal, we identified novel compound heterozygous variants in STN1 (previous gene symbol OBFC1): one loss‐of‐function––c.894dup (p.(Asp299Argfs*58)); and one missense––c.707T>C (p.(Leu236Pro)). Conclusion: Given the clinical phenotype and identified variants we suggest that this is only the fourth patient reported to date with CP due to mutations in STN1.
- Subjects :
- Male
Models, Molecular
0301 basic medicine
Pathology
leukodystrophy
Protein Conformation
DNA Mutational Analysis
030105 genetics & heredity
QH426-470
Compound heterozygosity
medicine.disease_cause
Leukoencephalopathies
Medicine
Coats' disease
Central Nervous System Cysts
Child
Genetics (clinical)
CLINICAL REPORTS
Mutation
Gastrointestinal tract
Brain Neoplasms
stn1
coats plus
Calcinosis
Phenotype
Pancytopenia
Retinal telangiectasia
Muscle Spasticity
CLINICAL REPORT
Heterozygote
medicine.medical_specialty
Telomere-Binding Proteins
Neuroimaging
Structure-Activity Relationship
03 medical and health sciences
Retinal Diseases
Seizures
Genetics
Humans
Genetic Predisposition to Disease
Molecular Biology
Alleles
Genetic Association Studies
business.industry
Leukodystrophy
medicine.disease
030104 developmental biology
Ataxia
Tomography, X-Ray Computed
business
Magnetic Resonance Angiography
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Acharya, T, Firth, H, Dugar, S, Grammatikopoulos, T, Seabra, L, Walters, A, Crow, Y J & Parker, A PJ 2021, ' Novel compound heterozygous STN1 variants are associated with Coats Plus syndrome ', Molecular Genetics and Genomic Medicine . https://doi.org/10.1002/mgg3.1708, Molecular Genetics & Genomic Medicine, Vol 9, Iss 12, Pp n/a-n/a (2021), Molecular Genetics & Genomic Medicine
- Accession number :
- edsair.doi.dedup.....5913a2d3c438b4be5290c7ce69f81d23