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 |
|---|---|
| Pages (from-to) | 54-63 |
| Number of pages | 10 |
| Journal | American Journal of Human Genetics |
| Volume | 77 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 1 2005 |
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ASJC Scopus subject areas
- Genetics
Cite this
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; Hejtmancik, J. Fielding; Schorderet, Daniel F.
In: American Journal of Human Genetics, Vol. 77, No. 1, 01.07.2005, p. 54-63.Research output: Contribution to journal › Article
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TY - JOUR
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
AU - Hejtmancik, J. Fielding
AU - Schorderet, Daniel F.
PY - 2005/7/1
Y1 - 2005/7/1
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.
UR - http://www.scopus.com/inward/record.url?scp=20544452085&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20544452085&partnerID=8YFLogxK
U2 - 10.1086/431346
DO - 10.1086/431346
M3 - Article
C2 - 15902656
AN - SCOPUS:20544452085
VL - 77
SP - 54
EP - 63
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 1
ER -