ABCA4 p.Gln636*
| ClinVar: |
c.1908G>T
,
p.Gln636His
?
, not provided
|
[switch to compact view]
Comments [show]
None has been submitted yet.
[hide] Molecular diagnosis of putative Stargardt disease ... BMC Med Genet. 2012 Aug 3;13:67. Strom SP, Gao YQ, Martinez A, Ortube C, Chen Z, Nelson SF, Nusinowitz S, Farber DB, Gorin MB
Molecular diagnosis of putative Stargardt disease probands by exome sequencing.
BMC Med Genet. 2012 Aug 3;13:67., [PMID:22863181]
Abstract [show]
ABSTRACT: BACKGROUND: The commonest genetic form of juvenile or early adult onset macular degeneration is Stargardt Disease (STGD) caused by recessive mutations in the gene ABCA4. However, high phenotypic and allelic heterogeneity and a small but non-trivial amount of locus heterogeneity currently impede conclusive molecular diagnosis in a significant proportion of cases. METHODS: We performed whole exome sequencing (WES) of nine putative Stargardt Disease probands and searched for potentially disease-causing genetic variants in previously identified retinal or macular dystrophy genes. Follow-up dideoxy sequencing was performed for confirmation and to screen for mutations in an additional set of affected individuals lacking a definitive molecular diagnosis. RESULTS: Whole exome sequencing revealed seven likely disease-causing variants across four genes, providing a confident genetic diagnosis in six previously uncharacterized participants. We identified four previously missed mutations in ABCA4 across three individuals. Likely disease-causing mutations in RDS/PRPH2, ELOVL, and CRB1 were also identified. CONCLUSIONS: Our findings highlight the enormous potential of whole exome sequencing in Stargardt Disease molecular diagnosis and research. WES adequately assayed all coding sequences and canonical splice sites of ABCA4 in this study. Additionally, WES enables the identification of disease-related alleles in other genes. This work highlights the importance of collecting parental genetic material for WES testing as the current knowledge of human genome variation limits the determination of causality between identified variants and disease. While larger sample sizes are required to establish the precision and accuracy of this type of testing, this study supports WES for inherited early onset macular degeneration disorders as an alternative to standard mutation screening techniques.
Comments [show]
None has been submitted yet.
No. Sentence Comment
77 STGD-02 15 Female 20/160 20/100 Few yellowish Flecks without autofluorescence Normal rod Normal cone Abnormal p.Q636X p.G1961E* .
X
ABCA4 p.Gln636* 22863181:77:112
status: NEW106 The second variant p.Q636X introduces a premature termination codon and is thus considered very likely deleterious.
X
ABCA4 p.Gln636* 22863181:106:21
status: NEW155 Of the five total disease-causing ABCA4 alleles found by WES, four (all except p.Q636X) have previously been described and are genotyped by the current ABCR array available from Asper Biotech, supporting the use of the genotyping array as a first-pass screening tool due to its low cost.
X
ABCA4 p.Gln636* 22863181:155:81
status: NEW