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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Acknowledgments
We thank the patients and their family members for participation in this study. We also thank Dr. Sudha and Dr. Chandra Kumar for help in patient recruitment. This work was funded by the Indian Institute of Science, Bangalore. The authors declare that the experiments comply with the current laws of the country.
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The authors declare that they have no conflict of interest.
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V. C. Prabhakaran was deceased.
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Kumar, A., Duvvari, M.R., Prabhakaran, V.C. et al. A homozygous mutation in LTBP2 causes isolated microspherophakia. Hum Genet 128, 365–371 (2010). https://doi.org/10.1007/s00439-010-0858-8
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DOI: https://doi.org/10.1007/s00439-010-0858-8