Homozygosity mapping identifies a GALK1 mutation as the cause of autosomal recessive congenital cataracts in 4 adult siblings
OF Chacon-Camacho, B Buentello-Volante… - Gene, 2014 - Elsevier
OF Chacon-Camacho, B Buentello-Volante, R Velázquez-Montoya, R Ayala-Ramirez…
Gene, 2014•ElsevierObjective Monogenic congenital cataract is one of the most genetically heterogeneous
ocular conditions with almost 30 different genes involved in its etiology. In adult patients,
genotype–phenotype correlations are troubled by eye surgery during infancy and/or long-
term ocular complications. Here, we describe the molecular diagnosis of GALK1 deficiency
as the cause of autosomal recessive congenital cataract in a family from Costa Rica.
Methods Four affected siblings were included in the study. All of them underwent eye …
ocular conditions with almost 30 different genes involved in its etiology. In adult patients,
genotype–phenotype correlations are troubled by eye surgery during infancy and/or long-
term ocular complications. Here, we describe the molecular diagnosis of GALK1 deficiency
as the cause of autosomal recessive congenital cataract in a family from Costa Rica.
Methods Four affected siblings were included in the study. All of them underwent eye …
Objective
Monogenic congenital cataract is one of the most genetically heterogeneous ocular conditions with almost 30 different genes involved in its etiology. In adult patients, genotype–phenotype correlations are troubled by eye surgery during infancy and/or long-term ocular complications. Here, we describe the molecular diagnosis of GALK1 deficiency as the cause of autosomal recessive congenital cataract in a family from Costa Rica.
Methods
Four affected siblings were included in the study. All of them underwent eye surgery during the first decade but medical records were not available. Congenital cataract was diagnosed by report. Molecular analysis included genome wide homozygosity mapping using a 250 K SNP Affymetrix microarray followed by PCR amplification and direct nucleotide sequencing of candidate gene.
Results
Genome wide homozygosity mapping revealed a 6 Mb region of homozygosity shared by two affected siblings at 17q25. The GALK1 gene was included in this interval and direct sequencing of this gene revealed a homozygous c.1144C>T mutation (p.Q382*) in all four affected subjects.
Conclusions
This work demonstrates the utility of homozygosity mapping in the retrospective diagnosis of a family with congenital cataracts in which ocular surgery at early age, the lack of medical records, and the presence of long term eye complications, impeded a clear clinical diagnosis during the initial phases of evaluation.
Elsevier