A homozygous mutation in LTBP2 causes isolated microspherophakia

Arun Kumar, Maheswara R. Duvvari, Venkatesh C. Prabhakaran, Jyoti S. Shetty, Gowri J. Murthy, Susan H. Blanton

Research output: Contribution to journalArticle

42 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)365-371
Number of pages7
JournalHuman genetics
Volume128
Issue number4
DOIs
StatePublished - Oct 2010

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Kumar, A., Duvvari, M. R., Prabhakaran, V. C., Shetty, J. S., Murthy, G. J., & Blanton, S. H. (2010). A homozygous mutation in LTBP2 causes isolated microspherophakia. Human genetics, 128(4), 365-371. https://doi.org/10.1007/s00439-010-0858-8