title: Novel homozygous, heterozygous and hemizygous FRMD7 gene mutations segregated in the same consanguineous family with congenital X-linked nystagmus.
abstract: Congenital nystagmus (NYS) is characterized by bilateral, spontaneous, and involuntary movements of the eyeballs that most commonly presents between 2 and 6 months of life. To date, 44 different FRMD7 gene mutations have been found to be etiological factors for the NYS1 locus at Xq26-q27. The aim of this study was to find the FRMD7 gene mutations in a large eleven-generation Indian pedigree with 71 members who are affected by NYS. Mutation analysis of the entire coding region and splice junctions of the FRMD7 gene revealed a novel missense mutation, c.A917G, predicts a substitution of Arg for Gln at codon 305 (Q305R) within exon 10 of FRMD7. The mutation was detected in hemizygous males, and in homozygous and heterozygous states in affected female members of the family. This mutation was not detected in unaffected members of the family or in 100 unrelated control subjects. This mutation was found to be at a highly conserved residue within the FERM-adjacent domain in affected members of the family. Structure prediction and energetic analysis of wild-type FRMD7 compared with mutant (Q305R) revealed that this change in amino acid led to a change in secondary structure predicted to be an energetically unstable protein. The present study represents the first confirmation of FRMD7 gene mutations in a multigenerational Indian family and expands the mutation spectrum for this locus.
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School, 1 rue Michel Servet, Geneva, Switzerland. Radhakrishna.uppala@unige.ch
authors.forename: Uppala
authors.initials: U
authors.lastname: Radhakrishna
authors.forename: Uppala
authors.initials: U
authors.lastname: Ratnamala
authors.forename: Samuel
authors.initials: S
authors.lastname: Deutsch
authors.forename: Lucia
authors.initials: L
authors.lastname: Bartoloni
authors.forename: Murali R
authors.initials: MR
authors.lastname: Kuracha
authors.forename: Raminder
authors.initials: R
authors.lastname: Singh
authors.forename: Jasjit
authors.initials: J
authors.lastname: Banwait
authors.forename: Dhundy K
authors.initials: DK
authors.lastname: Bastola
authors.forename: Kaid
authors.initials: K
authors.lastname: Johar
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Nath
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D003241:Consanguinity; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics*; D005091:Exons; D005260:Female; D050172:Genes, X-Linked / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000453:epidemiology / Q000235:genetics*; D057898:Hemizygote; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D020417:Nystagmus, Congenital / Q000453:epidemiology / Q000235:genetics*; D016366:Open Reading Frames; D010375:Pedigree; D017433:Protein Structure, Secondary
chemical_list: D003598:Cytoskeletal Proteins; C516168:FRMD7 protein, human; D008565:Membrane Proteins