Abstract |
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.
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Authors | Arun Kumar, Maheswara R Duvvari, Venkatesh C Prabhakaran, Jyoti S Shetty, Gowri J Murthy, Susan H Blanton |
Journal | Human genetics
(Hum Genet)
Vol. 128
Issue 4
Pg. 365-71
(Oct 2010)
ISSN: 1432-1203 [Electronic] Germany |
PMID | 20617341
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- LTBP2 protein, human
- Latent TGF-beta Binding Proteins
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Topics |
- Amino Acid Sequence
- Base Sequence
- Chromosome Mapping
- Chromosomes, Human, Pair 14
(genetics)
- Consanguinity
- DNA Mutational Analysis
- Exons
(genetics)
- Eye Abnormalities
(genetics)
- Family Health
- Female
- Genetic Loci
(genetics)
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Homozygote
- Humans
- India
- Latent TGF-beta Binding Proteins
(genetics)
- Lens, Crystalline
(abnormalities)
- Male
- Molecular Sequence Data
- Mutation
- Pedigree
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