Identification ofCNGA3Mutations in 46 Families

Abstract

mutations were reported in a patient with Leber congenital amaurosis (LCA) 17 and in a few patients with severe progressive COD. 13,15,16 Other studies 14,18 have shown the occurrence of progressive cone degeneration in achromatopsia. These findings suggest that the CNGA3 mutation is a good candidate for achromatopsia and for other forms of retinal dystrophies. To date, the CNGA3 gene has not been systematically analyzed in Chinese patients with achromatopsia, CORDs, or LCA. This study used Sanger sequencing to analyze the coding exons and their adjacent intronic regions of CNGA3 in 267 Chinese unrelated probands with CODs or LCA. Methods Patients This study was approved by the institutional review board of the Zhongshan Ophthalmic Center, Guangzhou, China. Written informed consent was obtained from all participants or their guardians before the study. In total, 267 Chinese unrelated probands, including 138 families with CODs and 129 families with LCA, were selected from the genomic DNA repository established by our team at the Zhongshan Ophthalmic Center in 1996. Using a method described previously, 19 genomic DNA was prepared from venous leukocytes from the proband of each family and from some family members, as well as 96 unrelated healthy control subjects from a previous study. 20 Identification of CNGA3 Mutations in 46 Families Original Investigation Research

Mutation of ATF6 causes autosomal recessive achromatopsia

“…While the affected members of the CORD8 family had night blindness (Khaliq et al 2000 ), the affected individuals from our ACHM family had normal night vision. Mutations in four previously identified ACHM genes namely CNGA3 , CNGB3 , PDE6C and PDE6H can cause both ACHM and CORD (Huang et al 2013 ; Li et al 2014b ). However, negative results from Sanger sequencing of all exons of ATF6 using DNA samples of two affected individuals from the CORD8 family ruled out the involvement of ATF6 in the etiology of CORD.…”

Identification of novel mutations by targeted exome sequencing and the genotype-phenotype assessment of patients with achromatopsia

“…His healthy sister carried a heterozygous mutation (c.1074G > A, p.W358X). Both of these mutations were identified in previous studies [ 7 , 8 , 20 ]. In family 2, the proband F2-IV:1 harbored one homozygous mutation in CNGA3 (c.968C > A, p.A323D), as a result of being consanguineous to the F2 family.…”

“…Achromatopsia (ACHM) is a severe congenital autosomal recessive retinal disorder caused by loss of cone photoreceptors. Mutations in the CNGA3 gene are recognized as the most common causes of ACHM and cone-rod dystrophies in the Chinese population [ 8 ]. In our study, we report three distinct disease-causative CNGA3 mutations, including one novel variant and two known mutations, in two Chinese families with ACHM.…”

“…Mutations in CNGA3 and CNGB3 , which encode the α-subunit and β-subunit of the CNG, account for 25 % and 40–50 % of affected individuals in multiple ethnic groups, respectively [ 3 , 7 ]. Mutations in CNGA3 are considered the most common cause of ACHM and cone-rod dystrophies (CORDs) in Chinese, in which only cone photoreceptors are usually affected, although CNGA3 mutations have been reported in a patient with CORDs and Leber congenital amaurosis (LCA) [ 8 , 9 ]. However, approximately 20–30 % of ACHM cases appear to lack pathogenic mutations, which is likely due to the limitations in the number of screened regions [ 1 , 3 – 5 , 10 ].…”

Epidemiologic, clinical and pathogenesis features of achromatopsia in the Russian population

“…Анализ сегрегации/родословной проводился с использованием доступной информации о членах семей согласно опубликованному протоколу [29].…”