Mutations in PIP5K3 are associated with François-Neetens mouchetée fleck corneal dystrophy.
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.
Li
Shouling
S
Ophthalmic Genetics and Clinical Services Branch, National Eye Institute, Bethesda, MD, USA.
Tiab
Leila
L
Jiao
Xiaodong
X
Munier
Francis L
FL
Zografos
Leonidas
L
Frueh
Béatrice E
BE
Sergeev
Yuri
Y
Smith
Janine
J
Rubin
Benjamin
B
Meallet
Mario A
MA
Forster
Richard K
RK
Hejtmancik
J Fielding
JF
Schorderet
Daniel F
DF
D001483:Base Sequence; D002889:Chromosomes, Human, Pair 2; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008958:Models, Molecular; D009154:Mutation; D010375:Pedigree; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*
D019869:Phosphatidylinositol 3-Kinases; C492139:PIKFYVE protein, human