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An Augmented ABCA 4 Screen Targeting Noncoding Regions Reveals a Deep Intronic Founder Variant in B elgian S targardt Patients
Author(s) -
Bauwens Miriam,
De Zaeytijd Julie,
Weisschuh Nicole,
Kohl Susanne,
Meire Françoise,
Dahan Karin,
Depasse Fanny,
De Jaegere Sarah,
De Ravel Thomy,
De Rademaeker Marjan,
Loeys Bart,
Coppieters Frauke,
Leroy Bart P.,
De Baere Elfride
Publication year - 2015
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22716
Subject(s) - abca4 , stargardt disease , biology , genetics , phenotype , mutation , founder effect , coding region , haplotype , gene , genotype
Autosomal‐recessive S targardt disease ( STGD 1) is hallmarked by a large proportion of patients with a single heterozygous causative variant in the disease gene ABCA 4 . Braun et al. ([Braun TA, 2013]) reported deep intronic variants of ABCA 4 in STGD 1 patients with one coding variant, prompting us to perform an augmented screen in 131 B elgian STGD 1 patients with one or no ABCA 4 variant to uncover deep intronic causal ABCA 4 variants. This revealed a second variant in 28.6% of cases. Twenty‐six percent of these carry the same causal variant c.4539+2001 G > A ( V 4). Haplotyping in V 4 carriers showed a common region of 63 kb, suggestive of a founder mutation. Genotype–phenotype correlations suggest a moderate‐to‐severe impact of V 4 on the STGD 1 phenotype. In conclusion, V 4 occurs in a high fraction of B elgian STGD 1 patients and represents the first deep intronic founder mutation in ABCA 4 . This emphasizes the importance of augmented molecular genetic testing of ABCA 4 in B elgian STGD 1.