Novel Intragenic<i>FRMD7</i>Deletion in a Pedigree with Congenital X-Linked Nystagmus

Fingert, John H.; Roos, Ben R.; Eyestone, M. E.; Pham, J. D.; Mellot, Mei L.; Stone, Edwin M

doi:10.3109/13816810903584989

Cited by 14 publications

(13 citation statements)

References 15 publications

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“…Mutations of FRMD7 are the major etiological contributor of ICN (1)(2)(3)(4)(5). A previous study by the current authors demonstrated that FRMD7 interacts with RhoGDI, whereby it specifically activates the Rac1 signalling involved in neuronal development.…”

Section: Discussionmentioning

confidence: 99%

“…There are currently no effective treatments for ICN and patients experience a significant decrease in their quality of life over time. To date, >40 mutations of FRMD7 have been detected worldwide in people from various ethnic backgrounds (1)(2)(3)(4)(5)(7)(8)(9). A previous study by the current authors identified two novel missense mutations (c.781C>G and c.886G>C) and a truncated mutation (c.1003C>T) of human FRMD7 in three X-linked ICN pedigrees (3).…”

Section: Introductionmentioning

confidence: 99%

“…It has been demonstrated that mutations in the FERM domain containing protein 7 (FRMD7) gene is one of the major causes of X-linked idiopathic congenital nystagmus (ICN) (1)(2)(3)(4)(5). ICN is an oculomotor disorder arising from a primary defect in the regions related to ocular motor control.…”

Section: Introductionmentioning

confidence: 99%

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Stable cell lines of human SH-SY5Y uniformly expressing wild-type or mutant-type FERM domain containing 7 gene

Mao

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. It has been reported that FERM domain containing 7 (FRMD7) may cause X-linked idiopathic congenital nystagmus (ICN). A total of >40 mutations of the FRMD7 gene have been identified, however their pathogenic role remains unclear. In the present study, enhanced green fluorescent protein-tagged wild-type (WT) and mutant (MT) FRMD7 (c. C781>G) were expressed in stably expressing human neuroblastoma SH-SY5Y cells following viral transfection and antibiotic selection. Uniform expression of the FRMD7 fusion proteins was confirmed via fluorescence microscopy and western blotting. The expression profiles of neuron-specific proteins and Rho guanine triphosphatases (GTPases) differed significantly between the wild-type and mutant cell lines. Levels of Mtap2, NF-M, nestin, GAP43 and Rac1 mRNA were significantly increased in MT-FRMD7 cells compared with controls (P<0.01). However, the expression of Rac1 protein did not differ significantly among the two cell lines. Taken together, the results of the current study suggest that MT-FRMD7 influences the expression of neuron-specific genes and Rho GTPases, which may be involved in the pathogenesis of ICN. The FRMD7 stable expression cell line may facilitate future studies investigating the role of this protein in neuronal development.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Stable cell lines of human SH-SY5Y uniformly expressing wild-type or mutant-type FERM domain containing 7 gene

Mao

et al. 2017

Experimental and Therapeutic Medicine

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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%

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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“…[345678] Mutations in FRMD7 gene are the major causes of Chinese familial X-linked CN and account for approximately 47% of Chinese patients with the disorder. [9]…”

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confidence: 99%

A previously unidentified deletion in G protein-coupled receptor 143 causing X-linked congenital nystagmus in a Chinese family

Liu

Jia

Wang

et al. 2016

Indian J Ophthalmol

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Background:Congenital nystagmus (CN) is characterized by conjugated, spontaneous, and involuntary ocular oscillations. It is an inherited disease and the most common inheritance pattern is X-linked CN. In this study, our aim is to identify the disease-causing mutation in a large sixth-generation Chinese family with X-linked CN.Methods:It has been reported that mutations in four-point-one, ezrin, radixin, moesin domain-containing 7 gene (FRMD7) and G protein-coupled receptor 143 gene (GPR143) account for the majority patients of X-linked nystagmus. We collected 8 ml blood samples from members of a large sixth-generation pedigree with X-linked CN and 100 normal controls. FRMD7 and GPR143 were scanned by polymerase chain reaction (PCR)-based DNA sequencing assays, and multiplex PCR assays were applied to detect deletions.Results:We identified a previously unreported deletion covering 7 exons in GPR143 in a Chinese family. The heterozygous deletion from exon 3 to exon 9 of GPR143 was detected in all affected males in the family, while it was not detected in other unaffected relatives or 100 normal controls.Conclusions:This is the first report of molecular characterization in GPR143 gene in the CN family. Our results expand the spectrum of GPR143 mutations causing CN and further confirm the role of GPR143 in the pathogenesis of CN.

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Novel IntragenicFRMD7Deletion in a Pedigree with Congenital X-Linked Nystagmus

Abstract: A range of missense, nonsense, frameshift, and splicing mutations in FRMD7 have been shown to cause X-linked congenital nystagmus. Here we show for the first time that large intragenic deletions of FRMD7 can also cause this form of nystagmus.

Cited by 14 publications

References 15 publications

Stable cell lines of human SH-SY5Y uniformly expressing wild-type or mutant-type FERM domain containing 7 gene

Stable cell lines of human SH-SY5Y uniformly expressing wild-type or mutant-type FERM domain containing 7 gene

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

A previously unidentified deletion in G protein-coupled receptor 143 causing X-linked congenital nystagmus in a Chinese family

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