title: Genetic heterogeneity and clinical outcome in a Swedish family with retinal degeneration caused by mutations in CRB1 and ABCA4 genes.
abstract: Genetic mechanisms underlying severe retinal dystrophy in a large Swedish family presenting two distinct phenotypes, Leber congenital amaurosis and Stargardt disease were investigated. In the family, four patients with Leber congenital amaurosis were homozygous for a novel c.2557C>T (p.Q853X) mutation in the CRB1 gene, while of two cases with Stargardt disease, one was homozygous for c.5461-10T>C in the ABCA4 gene and another was a compound heterozygous for c.5461-10T>C and a novel ABCA4 mutation c.4773+3 A>G. Sequence analysis of the entire ABCA4 gene in patients with Stargardt disease revealed complex alleles with additional sequence variants.Our results provide evidence of genetic complexity causative of different clinical features present in the same family, which is an obvious challenge for ophthalmologists, molecular geneticists and genetic counsellors.
authors.affiliation: Department of Medical Biosciences/Medical and Clinical Genetics, University Hospital of Umeå, SE 901 85, Umeå, Sweden, frida.jonsson@medbio.umu.se.
authors.forename: Frida
authors.initials: F
authors.lastname: Jonsson
authors.forename: Marie S
authors.initials: MS
authors.lastname: Burstedt
authors.forename: Ola
authors.initials: O
authors.lastname: Sandgren
authors.forename: Anna
authors.initials: A
authors.lastname: Norberg
authors.forename: Irina
authors.initials: I
authors.lastname: Golovleva
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D002648:Child; D005136:Eye Proteins / Q000235:genetics*; D005192:Family Health; D005260:Female; D018740:Genetic Heterogeneity; D006239:Haplotypes; D006801:Humans; D057130:Leber Congenital Amaurosis / Q000235:genetics*; D008268:Macular Degeneration / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D000080362:Stargardt Disease; D013548:Sweden
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; C448939:CRB1 protein, human; D005136:Eye Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins