title: ALMS1 null mutations: a common cause of Leber congenital amaurosis and early-onset severe cone-rod dystrophy.
abstract: 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.
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Y
authors.identifier: http://orcid.org/0000-0001-8760-2554
authors.initials: Y
authors.lastname: Xu
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: L
authors.initials: L
authors.lastname: Guan
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Xiao
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: H
authors.initials: H
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Jia
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Guo
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
keywords: Alström syndrome; Leber congenital amaurosis; Sanger sequencing; cone-rod dystrophy; null mutations; whole exome sequencing