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Homozygosity mapping identifies a GALK1 mutation as the cause of autosomal recessive congenital cataracts in 4 adult siblings.
Gene. 2014 Jan 25; 534(2):218-21.GENE

Abstract

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 250K SNP Affymetrix microarray followed by PCR amplification and direct nucleotide sequencing of candidate gene.

RESULTS

Genome wide homozygosity mapping revealed a 6Mb 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.

Authors+Show Affiliations

Research Unit-Genetics, Institute of Ophthalmology, "Conde de Valenciana", Mexico City, Mexico.Research Unit-Genetics, Institute of Ophthalmology, "Conde de Valenciana", Mexico City, Mexico.Cornea Department, "Dra. Olga Montoya" Ophthalmic Center, San Jose, Costa Rica.Research Unit-Genetics, Institute of Ophthalmology, "Conde de Valenciana", Mexico City, Mexico.Research Unit-Genetics, Institute of Ophthalmology, "Conde de Valenciana", Mexico City, Mexico; Department of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico. Electronic address: jczenteno@institutodeoftalmologia.org.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24211322

Citation

Chacon-Camacho, Oscar F., et al. "Homozygosity Mapping Identifies a GALK1 Mutation as the Cause of Autosomal Recessive Congenital Cataracts in 4 Adult Siblings." Gene, vol. 534, no. 2, 2014, pp. 218-21.
Chacon-Camacho OF, Buentello-Volante B, Velázquez-Montoya R, et al. Homozygosity mapping identifies a GALK1 mutation as the cause of autosomal recessive congenital cataracts in 4 adult siblings. Gene. 2014;534(2):218-21.
Chacon-Camacho, O. F., Buentello-Volante, B., Velázquez-Montoya, R., Ayala-Ramirez, R., & Zenteno, J. C. (2014). Homozygosity mapping identifies a GALK1 mutation as the cause of autosomal recessive congenital cataracts in 4 adult siblings. Gene, 534(2), 218-21. https://doi.org/10.1016/j.gene.2013.10.057
Chacon-Camacho OF, et al. Homozygosity Mapping Identifies a GALK1 Mutation as the Cause of Autosomal Recessive Congenital Cataracts in 4 Adult Siblings. Gene. 2014 Jan 25;534(2):218-21. PubMed PMID: 24211322.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Homozygosity mapping identifies a GALK1 mutation as the cause of autosomal recessive congenital cataracts in 4 adult siblings. AU - Chacon-Camacho,Oscar F, AU - Buentello-Volante,Beatriz, AU - Velázquez-Montoya,Roberto, AU - Ayala-Ramirez,Raul, AU - Zenteno,Juan C, Y1 - 2013/11/07/ PY - 2013/09/18/received PY - 2013/10/14/revised PY - 2013/10/25/accepted PY - 2013/11/12/entrez PY - 2013/11/12/pubmed PY - 2014/4/18/medline KW - BRLMM KW - Bayesian Robust Linear Model with Mahalanobis distance classifier KW - C KW - Cataract KW - DNA KW - GALE KW - GALK1 KW - GALT KW - Galactosemia KW - Homozygosity mapping KW - Mb KW - Ng KW - OMIM KW - On line Mendelian Inheritance in Man KW - PCR KW - Q KW - SNPs KW - T KW - UDP-galactose-4′-epimerase KW - cytosine KW - desoxyribonucleic acid KW - galactokinase KW - galactose-1-phosphate uridyltransferase KW - glutamine KW - megabase KW - nanogram KW - polymerase chain reaction KW - single nucleotide polymorphisms KW - thymine SP - 218 EP - 21 JF - Gene JO - Gene VL - 534 IS - 2 N2 - 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 250K SNP Affymetrix microarray followed by PCR amplification and direct nucleotide sequencing of candidate gene. RESULTS: Genome wide homozygosity mapping revealed a 6Mb 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. SN - 1879-0038 UR - https://www.unboundmedicine.com/medline/citation/24211322/Homozygosity_mapping_identifies_a_GALK1_mutation_as_the_cause_of_autosomal_recessive_congenital_cataracts_in_4_adult_siblings_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-1119(13)01466-2 DB - PRIME DP - Unbound Medicine ER -