Mutations in PIP5K3 are associated with François-Neetens mouchetée fleck corneal dystrophy

Shouling Li, Leila Tiab, Xiaodong Jiao, Francis L. Munier, Leonidas Zografos, Béatrice E. Frueh, Yuri Sergeev, Janine Smith, Benjamin Rubin, Mario A. Meallet, Richard K. Forster, J. Fielding Hejtmancik, Daniel F. Schorderet

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

François-Neetens fleck corneal dystrophy (CFD) is a rare, autosomal dominant corneal dystrophy characterized by numerous small white flecks scattered in all layers of the stroma. Linkage analysis localized CFD to a 24-cM (18-Mb) interval of chromosome 2q35 flanked by D2S2289 and D2S126 and containing PIP5K3. PIP5K3 is a member of the phosphoinositide 3-kinase family and regulates the sorting and traffic of peripheral endosomes that contain lysosomally directed fluid phase cargo, by controlling the morphogenesis and function of multivesicular bodies. Sequencing analysis disclosed missense, frameshift, and/or protein-truncating mutations in 8 of 10 families with CFD that were studied, including 2256delA, 2274delCT, 2709C→T (R851X), 3120C→T (Q988X), IVS19-1G→C, 3246G→T (E1030X), 3270C→T (R1038X), and 3466A→G (K1103R). The histological and clinical characteristics of patients with CFD are consistent with biochemical studies of PIP5K3 that indicate a role in endosomal sorting.

Original languageEnglish (US)
Pages (from-to)54-63
Number of pages10
JournalAmerican journal of human genetics
Volume77
Issue number1
DOIs
StatePublished - Jul 2005

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Li, S., Tiab, L., Jiao, X., Munier, F. L., Zografos, L., Frueh, B. E., Sergeev, Y., Smith, J., Rubin, B., Meallet, M. A., Forster, R. K., Hejtmancik, J. F., & Schorderet, D. F. (2005). Mutations in PIP5K3 are associated with François-Neetens mouchetée fleck corneal dystrophy. American journal of human genetics, 77(1), 54-63. https://doi.org/10.1086/431346