Skewed X inactivation in an X linked nystagmus family resulted from a novel, p.R229G, missense mutation in the FRMD7 gene

Kaplan, Yüksel; Vargel, İbrahim; Kansu, Tülay; Akin, Burcu; Rohmann, Edyta; Kamaci, Soner; Uz, Elif; Özçelık, Tayfun; Wollnik, Bernd; Akarsu, Nurten

doi:10.1136/bjo.2007.128157

Cited by 19 publications

(14 citation statements)

References 14 publications

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“…At least six genetic loci for CMN have been suggested, including three loci for autosomal dominant CMN (NYS2, MIM 164100, 6p12;NYS3, MIM 608345, 7p11;NYS4, MIM 193003, 13q) (Kerrison et al 1996;Klein et al 1998;Patton et al 1993;Ragge et al 2003) and three loci for X-linked CMN (NYS1, MIM 310700, Xq26-q27;NYS5, MIM 300589, Xp11.4-11.3;NYS6, MIM 300814, Xp22.3) (Cabot et al 1999;Kerrison et al 1999;Liu et al 2007). Mutation in FRMD7 has been identiWed as the most common cause of X-linked CMN (He et al 2008;Kaplan et al 2008;Schorderet et al 2007;Self et al 2007;Shiels et al 2007;Tarpey et al 2006;Zhang et al 2007a, b). In large families with CMN, the condition is usually transmitted as an X-linked trait, but is occasionally reported as an autosomal dominant trait, which has hindered the search for additional loci and genes.…”

Section: Introductionmentioning

confidence: 99%

A novel locus for autosomal dominant congenital motor nystagmus mapped to 1q31-q32.2 between D1S2816 and D1S2692

Xiao

Guo

et al. 2011

Hum Genet

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Congenital motor nystagmus (CMN) is characterized by bilateral involuntary ocular oscillation without any other underlying ocular or systemic diseases. An autosomal dominant CMN was identified in a large Chinese family where all patients had nystagmus since infancy. The nystagmus in the family is independent of any known ocular or systemic diseases. After exclusion of known CMN loci, a genome-wide scan was performed by genotyping microsatellite markers at about 10 cM intervals, together with two-point linkage analysis. Exome sequencing was used to screen coding exons of well-annotated genes. Sanger-dideoxy sequencing was used to verify candidate variations inside the linkage interval. Congenital motor nystagmus in this family shows linkage to markers in a 11.39 Mb (12.1 cM) region on chromosome 1q31-q32.2 between D1S2816 and D1S2692. All nine markers in the linkage interval gave positive lod scores, with D1S2655 and D1S2636 yielding lod scores of 5.16 and 5.18, respectively, at θ = 0. No causative mutation in the linkage interval was identified by exome sequencing of gDNA from four patients. A linkage study of additional families and further analysis of candidate genes may ultimately lead to identification of the gene responsible for dominantly inherited CMN.

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Section: Introductionmentioning

confidence: 99%

A novel locus for autosomal dominant congenital motor nystagmus mapped to 1q31-q32.2 between D1S2816 and D1S2692

Xiao

Guo

et al. 2011

Hum Genet

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“…The conserved ezrin/radixin/ moesin (ERM) proteins often organize membranecytoskeletal interactions (Tsukita and Yonemura, 1999), and share a C-terminal actin-binding domain and an N-terminal FERM domain that binds membrane proteins (Mcclatchey and Fehon, 2009), also acting as scaffolding for adaptor and signaling molecules (Mcclatchey and Fehon, 2009). (Tarpey et al, 2006;Schorderet et al, 2007;Self et al, 2007;Shiels et al, 2007;Zhang B. et al, 2007;He et al, 2008a;Kaplan et al, 2008;Li et al, 2008a;Du et al, 2011;Khan et al, 2011;Thomas et al, 2011;Hu et al, 2012;Radhakrishna et al, 2012) and the novel mutation in this study within FRMD7 has been indicated (Note: for interpretation of the references to color in this figure legend, the reader is referred to the web version of this article)…”

Section: Discussionmentioning

confidence: 90%

“…3) (Tarpey et al, 2006;Schorderet et al, 2007;Self et al, 2007;Shiels et al, 2007;Zhang B. et al, 2007;He et al, 2008a;Kaplan et al, 2008;Li et al, 2008a;Du et al, 2011;Khan et al, 2011;Thomas et al, 2011;Hu et al, 2012;Radhakrishna et al, 2012). These mutations include missense, nonsense, splicing mutations, insertions, and deletions.…”

Section: Discussionmentioning

confidence: 99%

Novel mutation c.980_983delATTA compound with c.986C>A mutation of the FRMD7 gene in a Chinese family with X-linked idiopathic congenital nystagmus

Song

Chen

Sun

et al. 2013

J. Zhejiang Univ. Sci. B

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Abstract:Objective: To screen mutations in FERM domain-containing protein 7 (FRMD7) gene in two Chinese families with X-linked idiopathic congenital nystagmus (XLICN). Methods: Common ophthalmic data and peripheral blood of two Chinese XLICN families (families A and B) were collected after informed consent. Genomic DNA was prepared from the peripheral blood of members of the two families and from 100 normal controls. Mutations in the FRMD7 gene were determined by directly sequencing polymerase chain reaction (PCR) products. Results: We identified a novel mutation c.980_983delATTA compound with c.986C>A mutation in the 11th exon of FRMD7 in family B, and a previously reported splicing mutation c.782G>C (p.R261G) in family A. The mutations were detected in patients and female carriers, while they were absent in other relatives or in the 100 normal controls. Conclusions: Our results expand the spectrum of FRMD7 mutations in association with XLICN, and further confirm that the mutations of FRMD7 are the underlying molecular mechanism for XLICN.

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“…9 To date, 44 FRMD7 gene mutations have been identified in various NYS families suggesting that this gene has an important role in the NYS development. [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] The majority of these mutations were clustered in the highly conserved FERM-C domain in exons of 7-9 ( Table 1). …”

Section: Resultsmentioning

confidence: 99%

“…This is consistent with a previously published report. 25 The clinical significance of hemi/homozygous as compared with heterozygous mutation is not yet known, although Kaplan et al 13 found a missense mutation, R229G, in the FRMD7 gene in heterozygous and homozygous condition in members of a large X-linked NYS family without phenotypic variation. The location of the present residues is highly conserved in multiple species (Figure 1c) suggesting that the mutation at codon 305 is likely to have a significant effect on FRMD7 protein functionality.…”

Section: Resultsmentioning

confidence: 99%

Novel homozygous, heterozygous and hemizygous FRMD7 gene mutations segregated in the same consanguineous family with congenital X-linked nystagmus

et al. 2012

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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 FERMadjacent 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.

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Skewed X inactivation in an X linked nystagmus family resulted from a novel, p.R229G, missense mutation in the FRMD7 gene

Cited by 19 publications

References 14 publications

A novel locus for autosomal dominant congenital motor nystagmus mapped to 1q31-q32.2 between D1S2816 and D1S2692

A novel locus for autosomal dominant congenital motor nystagmus mapped to 1q31-q32.2 between D1S2816 and D1S2692

Novel mutation c.980_983delATTA compound with c.986C>A mutation of the FRMD7 gene in a Chinese family with X-linked idiopathic congenital nystagmus

Novel homozygous, heterozygous and hemizygous FRMD7 gene mutations segregated in the same consanguineous family with congenital X-linked nystagmus

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