A homozygous mutation in LTBP2 causes isolated microspherophakia

Kumar, Arun and Duvvari, Maheswara R and Prabhakaran, Venkatesh C and Shetty, Jyoti S and Murthy, Gowri J and Blanton, Susan Halloran (2010) A homozygous mutation in LTBP2 causes isolated microspherophakia. In: Human Genetics, 128 (4). pp. 365-371.

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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.

Item Type:	Journal Article
Publication:	Human Genetics
Publisher:	Springer
Additional Information:	Copyright of this article belongs to Springer.
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	26 Oct 2010 09:19
Last Modified:	26 Oct 2010 09:19
URI:	http://eprints.iisc.ac.in/id/eprint/33432

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