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ALMS1 null mutations: a common cause of Leber congenital amaurosis and early‐onset severe cone–rod dystrophy
Author(s) -
Xu Y.,
Guan L.,
Xiao X.,
Zhang J.,
Li S.,
Jiang H.,
Jia X.,
Yin Y.,
Guo X.,
Wang J.,
Zhang Q.
Publication year - 2016
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12617
Subject(s) - proband , sanger sequencing , compound heterozygosity , exome sequencing , genetics , mutation , medicine , candidate gene , retinal degeneration , gucy2d , biology , gene , receptor , guanylate cyclase , guanylate cyclase 2c
In our previous studies, mutations in known candidate genes were detected in approximately 50% of Chinese patients with various forms of retinal degeneration. The next stage, identifying additional causative mutations in patients with various forms of genetic eye diseases based on whole exome sequencing of 1220 samples, revealed frequent homozygous or compound heterozygous null mutations in ALMS1 , which are known to associate with Alström syndrome as well as individuals diagnosed with Leber congenital amaurosis ( LCA ) or early‐onset severe cone–rod dystrophy ( CORD ) without signs of systemic phenotypes except that one had a congenital heart abnormity. Sanger sequencing, co‐segregation analysis and analysis of normal individuals identified a total of 13 null mutations in ALMS1 in 11 probands, including 4 probands with homozygous mutations and 7 with compound heterozygous mutations. Follow‐up examinations revealed absent or mild systemic manifestations of Alström syndrome in those available: 9 of 15 patients in 11 families. These findings not only expand the spectrum of phenotypes associated with ALMS1 mutations but also suggest that ALMS1 should be regarded as a candidate causative gene in patients diagnosed with isolated LCA and early‐onset severe CORD .