To investigate the disease-causing mutation in a family with Leber congenital amaurosis (LCA).

A Chinese Han pedigree with LCA from Chaoshan area was recruited in Shantou International Eye Center in August 2011.The clinical features of the families were evaluated, including medical history, best corrected visual acuity, intraocular pressure and fundus photography.The peripheral blood sample of 5 ml was collected from each of the family members for the extraction of genomic DNA.DNA of the proband was investigated by whole exome sequencing (WES) and was filtered for function of variants and inheritance pattern.Then, Sanger sequencing was performed to confirm the WES result on all the participating subjects in the pedigree.

There were 11 families of 3 generations in this pedigree, and 2 female LCA patients were found (Ⅱ2 and Ⅱ4) who were sisters.The parents (Ⅰ-1 and Ⅰ-2) and children (Ⅲ-1, Ⅲ-2, Ⅲ-3 and Ⅲ-4) of the patients showed normal phenotype, suggesting an autosomal recessive pattern.The patients appeared severe visual impairment during early childhood.Ophthalmic examination showed diffuse pigmentation on the retina and attenuation of retinal artery in both patients.WES of proband revealed two compound heterozygous mutations (c.2234C>T, p.T745M; c. 3488G>T, p.C1163F) of the CRB1 gene.Sanger sequencing confirmed the mutations in both patients (Ⅱ-2 and Ⅲ-4), and the parents of the patients were found to carry one mutations respectively and the other subjects with normal phenotype had neither none or only one mutation.

The compound heterozygous mutation of c. 2234C>T, p.T745M and c. 3488G>T, p.C1163F in CRB1 is responsible for LCA pathogenesis this Chinese Han pedigree.

Leber congenital amaurosis; Whole exome sequencing; Compound heterozygous mutation; CRB1 gene; Pedigree