ABCA3 p.Leu326Pro
| ClinVar: |
c.977T>C
,
p.Leu326Pro
D
, Pathogenic
|
| Predicted by SNAP2: | A: N (53%), C: N (66%), D: D (66%), E: N (57%), F: N (66%), G: D (66%), H: N (57%), I: N (93%), K: D (59%), M: N (93%), N: D (53%), P: D (59%), Q: N (61%), R: D (59%), S: N (53%), T: N (66%), V: N (82%), W: D (63%), Y: N (61%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: N, W: D, Y: D, |
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[hide] Mutations in the ABCA3 gene are associated with ca... Invest Ophthalmol Vis Sci. 2014 Nov 18;55(12):8031-43. doi: 10.1167/iovs.14-14098. Chen P, Dai Y, Wu X, Wang Y, Sun S, Xiao J, Zhang Q, Guan L, Zhao X, Hao X, Wu R, Xie L
Mutations in the ABCA3 gene are associated with cataract-microcornea syndrome.
Invest Ophthalmol Vis Sci. 2014 Nov 18;55(12):8031-43. doi: 10.1167/iovs.14-14098., [PMID:25406294]
Abstract [show]
PURPOSE: Cataract-microcornea syndrome (CCMC) is an autosomal dominant inherited disease characterized by the association of congenital cataract and microcornea without any other systemic anomaly or dysmorphism. Although mutations of several genes have been shown to cause dominant CCMC, in many patients the causative gene has not yet been identified. Our aim was to identify the disease-associated gene in Chinese patients with CCMC. METHODS: The CCMC patients from two unrelated Chinese families and 26 sporadic patients were enrolled. All the patients were screened by Sanger sequencing with no identified mutations. Genetic variations were screened by whole-exome sequencing and then validated using Sanger sequencing. RESULTS: By sequencing the whole exome of three patients in a Chinese four-generation dominant CCMC family (Family A), three heterozygous missense mutation (c.115C>G, c.277G>A, and c.4393G>A) were identified in ATP-binding cassette protein A3 (ABCA3). At highly conserved positions, changes (c.115C>G and c.4393G>A) were predicted to have functional impacts and completely cosegregated with the phenotype. We further confirmed our finding by identifying another heterozygous missense mutation, c.2408C>T, in ABCA3 in an additional dominant CCMC family (Family B), which also cosegregated with the phenotype. Moreover, four heterozygous mutations, two missense mutations (c.4253A>T, c.2069A>T) and two splice site mutations (c.4053+2T>C, c.2765-1G>T) were identified from the sporadic patients. The ABCA3 protein was expressed in human lens capsule, choroid-retinal pigment epithelium and retinal pigment epithelial cells. CONCLUSIONS: Mutations in the human ABCA3 gene were associated with lethal respiratory distress. Our study showed, for the first time to our knowledge, that mutations in ABCA3 were associated with CCMC, warranting further investigations on the pathogenesis of this disorder.
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No. Sentence Comment
293 Genetic Variants Identified in ABCA3 in Patients With Surfactant Metabolism Dysfunction-3 (SMDP3) dbSNP rs# Cluster ID Codons Substitution Mutation Type Mutation Mode rs121909181 c.3426G>A W1142X Missense Homozygosity rs121909182 c.301T>C L101P Missense Homozygosity rs121909183 c.4657T>C L1553P Missense Homozygosity rs28936691 c.4772A>C Q1591P Missense Heterozygosity rs121909184 c.1702G>A N568D Missense Heterozygosity - c.4909&#fe;1G>A - Splice site Homozygosity rs121909185 c.977T>C L326P Missense Homozygosity 19.
X
ABCA3 p.Leu326Pro 25406294:293:488
status: NEW