title: Identifcation of a novel mutation p.I240T in the FRMD7 gene in a family with congenital nystagmus.
abstract: Congenital Nystagmus (CN) is a genetically heterogeneous ocular disease, which causes a significant proportion of childhood visual impairment. To identify the underlying genetic defect of a CN family, twenty-two members were recruited. Genotype analysis showed that affected individuals shared a common haplotype with markers flanking FRMD7 locus. Sequencing FRMD7 revealed a T > C transition in exon 8, causing a conservative substitution of Isoleucine to Tyrosine at codon 240. By protein structural modeling, we found the mutation may disrupt the hydrophobic core and destabilize the protein structure. We reviewed the literature and found that exons 2, 8, and 9 (11.4% of the sequence of FRMD7 mRNA) represent the majority (55.3%) of the reported FRMD7 mutations. In summary, we identified a novel mutation in FRMD7, showed its molecular consequence, and revealed the mutation-rich exons of the FRMD7 gene. Collectively, this provides molecular insights for future CN clinical genetic diagnosis and treatment.
authors.affiliation: 1] Department of Ophthalmology, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005 China [2].
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhu
authors.forename: Jianfu
authors.initials: J
authors.lastname: Zhuang
authors.forename: Xianglian
authors.initials: X
authors.lastname: Ge
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Ji
authors.initials: J
authors.lastname: Sun
authors.forename: Juhua
authors.initials: J
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
mesh_terms: D001483:Base Sequence; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005133:Eye Movements / Q000235:genetics; D005190:Family; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D020417:Nystagmus, Congenital / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment
chemical_list: D003598:Cytoskeletal Proteins; C516168:FRMD7 protein, human; D008565:Membrane Proteins