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

doi:10.1086/431346

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

Ophthalmology

Research output: Contribution to journal › Article

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 language	English (US)
Pages (from-to)	54-63
Number of pages	10
Journal	American journal of human genetics
Volume	77
Issue number	1
DOIs	https://doi.org/10.1086/431346
State	Published - Jul 2005

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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10.1086/431346

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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

Mutations in PIP5K3 are associated with François-Neetens mouchetée fleck corneal dystrophy. / Li, Shouling; Tiab, Leila; Jiao, Xiaodong; Munier, Francis L.; Zografos, Leonidas; Frueh, Béatrice E.; Sergeev, Yuri; Smith, Janine; Rubin, Benjamin; Meallet, Mario A.; Forster, Richard K.; Hejtmancik, J. Fielding; Schorderet, Daniel F.

In: American journal of human genetics, Vol. 77, No. 1, 07.2005, p. 54-63.

Research output: Contribution to journal › Article

Li, Shouling ; Tiab, Leila ; Jiao, Xiaodong ; Munier, Francis L. ; Zografos, Leonidas ; Frueh, Béatrice E. ; Sergeev, Yuri ; Smith, Janine ; Rubin, Benjamin ; Meallet, Mario A. ; Forster, Richard K. ; Hejtmancik, J. Fielding ; Schorderet, Daniel F. / Mutations in PIP5K3 are associated with François-Neetens mouchetée fleck corneal dystrophy. In: American journal of human genetics. 2005 ; Vol. 77, No. 1. pp. 54-63.

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title = "Mutations in PIP5K3 are associated with Fran{\c c}ois-Neetens mouchet{\'e}e fleck corneal dystrophy",

abstract = "Fran{\c c}ois-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.",

author = "Shouling Li and Leila Tiab and Xiaodong Jiao and Munier, {Francis L.} and Leonidas Zografos and Frueh, {B{\'e}atrice E.} and Yuri Sergeev and Janine Smith and Benjamin Rubin and Meallet, {Mario A.} and Forster, {Richard K.} and Hejtmancik, {J. Fielding} and Schorderet, {Daniel F.}",

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AU - Zografos, Leonidas

AU - Frueh, Béatrice E.

AU - Sergeev, Yuri

AU - Smith, Janine

AU - Rubin, Benjamin

AU - Meallet, Mario A.

AU - Forster, Richard K.

AU - Hejtmancik, J. Fielding

AU - Schorderet, Daniel F.

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AB - 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.

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