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 › peer-review

80 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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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 › peer-review

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.

@article{9c83b08f58f64c85b51c5ed3a4929aab,

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.}",

note = "Funding Information: We thank the members of the families, for their participation in this study, and C{\'e}line Agosti, Tatiana Favez, and Sylviane M{\'e}trailler, for their technical assistance. We acknowledge support from the Swiss National Science Foundation (grant 32-065250.01). ",

year = "2005",

month = jul,

doi = "10.1086/431346",

language = "English (US)",

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T1 - Mutations in PIP5K3 are associated with François-Neetens mouchetée fleck corneal dystrophy

AU - Li, Shouling

AU - Tiab, Leila

AU - Jiao, Xiaodong

AU - Munier, Francis L.

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.

N1 - Funding Information: We thank the members of the families, for their participation in this study, and Céline Agosti, Tatiana Favez, and Sylviane Métrailler, for their technical assistance. We acknowledge support from the Swiss National Science Foundation (grant 32-065250.01).

PY - 2005/7

Y1 - 2005/7

N2 - 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.

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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