Human Genetics

, Volume 128, Issue 4, pp 365–371

A homozygous mutation in LTBP2 causes isolated microspherophakia


    • Department of Molecular Reproduction, Development and GeneticsIndian Institute of Science
  • Maheswara R. Duvvari
    • Department of Molecular Reproduction, Development and GeneticsIndian Institute of Science
  • Venkatesh C. Prabhakaran
    • Minto Ophthalmic Hospital
  • Jyoti S. Shetty
    • Bangalore West Lions Superspecialty Eye Hospital
  • Gowri J. Murthy
    • Prabha Eye Clinic
  • Susan H. Blanton
    • Miami Institute for Human GenomicsUniversity of Miami Miller School of Medicine
Original Investigation

DOI: 10.1007/s00439-010-0858-8

Cite this article as:
Kumar, A., Duvvari, M.R., Prabhakaran, V.C. et al. Hum Genet (2010) 128: 365. doi:10.1007/s00439-010-0858-8


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.

Supplementary material

439_2010_858_MOESM1_ESM.doc (87 kb)
Supplementary material (DOC 87 kb)

Copyright information

© Springer-Verlag 2010