Novel ABCA4 Mutation In 3 Chinese Family With Stargardt Disease

Backgrounds and AimsStargardt disease is the most common juvenile macular dystrophy which is predominantly inherited as an autosomal recessive trait,although an autosomal dominant form has been also described.Studies determined that ABCA4 gene mutation is closely associated with Stargardt disease,but the mutation locus are varied.This study was to identify virulence mutation locus of ABCA4 gene of 3Chinese family pedigree with Stargardt disease.Material and MethodsPeripheral venous blood of 12 members from 3 families was collected.Genome DNA was extracted from samples of propositi to establish genomic library and exon and adjacent intron region of main disease-causing gene ABCA4,ELOVL4,PROM1 were acquired and enriched.After quality control,high-throughput sequencing and database comparison were carried out to locate suspected mutation.Finally,it was compared and confirmed by comparing with other members of the family and professional database to confirm mutation.ResultsA pair of compound heterozygous mutations in ABCA4 gene were found in each family.For the first family:(1)c.2894A>G,p.N965 S,a missense mutation,(2)c.101＿106del,p.34＿36del,a deletion mutation.For the second family:(1)c.5899-2A>G,a splicing mutation,(2)c.1222C>T,p.R408 X,a nonsense mutation.For the third family:(1)c.1982T>G,p.L661 R,a missense mutation,(2)c.101＿106del,p.34＿36del,a deletion mutation.Mutations of all patients have heterozygous mutation in the corresponding locus of their parents.ConclusionsIn this study,c.101＿106del&c.2894A>G,c.5899-2A>G&c.1222C>T and c.1982T>G&c.101＿106del in ABCA4 gene are pathogenicity mutations from three Stargardt families,among which,c.2894A>G was reported to be related with Stargardt Disease in HGMD professional database and others are all new mutations.It has amplified ABCA4 mutation spectrum.