A homozygous mutation in LTBP2 causes isolated microspherophakia
| Autor: | Jyoti S Shetty, Maheswara R Duvvari, Venkatesh C. Prabhakaran, Gowri J Murthy, Susan H. Blanton, Arun Kumar |
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| Rok vydání: | 2010 |
| Předmět: |
Marfan syndrome
Male Genetics and epigenetic pathways of disease [NCMLS 6] DNA Mutational Analysis Molecular Sequence Data India Locus (genetics) Biology Genomic disorders and inherited multi-system disorders [IGMD 3] Exon Consanguinity Gene duplication Lens Crystalline Genetics medicine Humans Genetic Predisposition to Disease Amino Acid Sequence Eye Abnormalities Gene Genetics (clinical) Chromosomes Human Pair 14 Family Health Base Sequence Genetic heterogeneity Homozygote Chromosome Mapping Exons medicine.disease Pedigree Microspherophakia Latent TGF-beta Binding Proteins Genetic Loci Mutation Female Congenital disorder Genome-Wide Association Study |
| Zdroj: | Human Genetics, 128, 4, pp. 365-71 Human Genetics, 128, 365-71 |
| ISSN: | 1432-1203 0340-6717 |
| Popis: | Item does not contain fulltext Microspherophakia is an autosomal-recessive congenital disorder characterized by small spherical lens. It may be isolated or occur as part of a hereditary systemic disorder, such as Marfan syndrome, autosomal dominant and recessive forms of Weill-Marchesani syndrome, autosomal dominant glaucoma-lens ectopia-microspherophakia-stiffness-shortness syndrome, autosomal dominant microspherophakia with hernia, and microspherophakia-metaphyseal dysplasia. The purpose of this study was to map and identify the gene for isolated microspherophakia in two consanguineous Indian families. Using a whole-genome linkage scan in one family, we identified a likely locus for microspherophakia (MSP1) on chromosome 14q24.1-q32.12 between markers D14S588 and D14S1050 in a physical distance of 22.76 Mb. The maximum multi-point lod score was 2.91 between markers D14S1020 and D14S606. The MSP1 candidate region harbors 110 reference genes. DNA sequence analysis of one of the genes, LTBP2, detected a homozygous duplication (insertion) mutation, c.5446dupC, in the last exon (exon 36) in affected family members. This homozygous mutation is predicted to elongate the LTBP2 protein by replacing the last 6 amino acids with 27 novel amino acids. Microspherophakia in the second family did not map to this locus, suggesting genetic heterogeneity. The present study suggests a role for LTBP2 in the structural stability of ciliary zonules, and growth and development of lens. 01 oktober 2010 |
| Databáze: | OpenAIRE |
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