Thrombospondin Mutations and Patients With Primary Congenital Glaucoma in a United States Population.
Boese Erin A, Alward Wallace L M, Kwon Young H, Roos Ben R, Stone Edwin M, Scheetz Todd E, Fingert John H
AI Summary
This study found THBS1 mutations are not a common cause of primary congenital glaucoma in a US population, suggesting they are a rare cause overall.
Abstract
Mutations in the thrombospondin 1 ( THBS1 ) gene have been previously reported in primary congenital glaucoma (PCG) pedigrees that exhibit autosomal dominant inheritance with low penetrance. We sought to determine the role of THBS1 mutations in a cohort of 20 patients with PCG and 362 normal controls from Iowa using a combination of Sanger sequencing and whole exome sequencing. We detected 16 different THBS1 variants, including 4 rare, nonsynonymous variants (p.Thr611Met, p.Asn708Lys, p.Gln1089His, and p.Glu1166Lys). However, none of these variants were judged to be disease-causing mutations based on: 1) prevalence in cases and controls from Iowa, 2) prevalence in the public database gnomAD, 3) mutation analysis algorithms, and 4) THBS1 DNA sequence conservation. These results indicate THBS1 mutations are not a common cause of PCG in patients from Iowa and may be a rare cause of PCG overall.
MeSH Terms
Shields Classification
Key Concepts4
A study of 20 patients with primary congenital glaucoma (PCG) and 362 normal controls from Iowa detected 16 different THBS1 variants, including 4 rare, nonsynonymous variants (p.Thr611Met, p.Asn708Lys, p.Gln1089His, and p.Glu1166Lys).
None of the 16 different THBS1 variants detected in a cohort of 20 patients with primary congenital glaucoma (PCG) and 362 normal controls from Iowa were judged to be disease-causing mutations based on prevalence in cases and controls from Iowa, prevalence in the public database gnomAD, mutation analysis algorithms, and THBS1 DNA sequence conservation.
THBS1 mutations are not a common cause of primary congenital glaucoma (PCG) in patients from Iowa and may be a rare cause of PCG overall, based on a study of 20 patients with PCG and 362 normal controls from Iowa.
Mutations in the thrombospondin 1 (THBS1) gene have been previously reported in primary congenital glaucoma (PCG) pedigrees that exhibit autosomal dominant inheritance with low penetrance.
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