A novel frameshift mutation in FRMD7 causes X-linked infantile nystagmus in a Chinese family

Abstract

BackgroundInfantile nystagmus (IN) is an oculomotor disorder that is characterized by conjugate involuntary, rapid and repetitive movement of the eyes. To date, the pathogenesis of IN remains unclear. Many patients show an X-linked inheritance pattern. In this study, we explored the mutation in the FERM domain-containing 7 (FRMD7) gene in a Chinese family with X-linked infantile nystagmus.MethodsWe conducted comprehensive ocular examinations and collected 5 ml of blood samples from members of a family with X-linked IN and 100 normal controls. Mutations in FRMD7 were identified by sequencing PCR products.ResultsWe found a 7-bp deletion(c.823-829delACCCTAC) in the 9th exon of FRMD7 in a Chinese family with IN, which predicted a truncation of the protein.ConclusionsThis study reported a novel mutation of the FRMD7 gene occurred in a Chinese family with IN, thus expanding the spectrum of FRMD7 mutations causing IN, and further confirming that the mutations of FRMD7 are the underlying molecular cause of IN.

Transcriptomics of Tasmanian Devil (Sarcophilus Harrisii) Ear Tissue Reveals Homogeneous Gene Expression Patterns across a Heterogeneous Landscape

“…Sex bias in the expression of FRMD7 , which was upregulated in female relative to male devils, has also been observed in sheep [55]. FRMD7 is primarily associated with eye movement, eye control, and neurite development [56,57], as well as a number of X-linked genetic disorders [58,59]. In addition to its role in eye development and movement, a subdomain of FRMD7 shares structural similarity to Acyl–CoA-binding proteins, which has interesting implications for epidermal functions [60].…”

“…The Acyl–CoA-binding protein is involved in fatty acid metabolism, which is crucial for hair and skin maintenance [61]. The interference of the expression of this protein has been shown to cause severe skin and hair abnormalities, even resulting in alopecia and scaling of skin [59]. Sex-based differences have also been observed in regard to DFTD, with females suffering less decline in overall body condition when infected [62] and having different SNPs associated with survival compared to males [12].…”

Ocular findings and genomics of X-linked recessive disorders: A review

“…Nystagmus 1, Congenital, X-linked is caused by mutations in the FRMD7 (OMIM # 300628) gene. [ 118 117 118 119 120 121 122 125 ] FRMD7 contains 12 exons and encodes a 714-amino-acid polypeptide known to be expressed in areas of the brain that control eye movement and in the retina. [ 121 ] Nystagmus 6, Congenital, X-linked is attribute to mutations in the GPR143 (Xp22.2) gene.…”

“…Ocular findings include typical horizontal (to-and-fro) eye movements with reports of vertical and rotary eye movements. [ 118 119 120 121 122 123 124 125 126 127 128 ] Decrease in nystagmus amplitude and increase in frequency of the nystagmus are observed as the patient grows older. Strabismus and amblyopia may often develop.…”

Clinical utility gene card for FRMD7-related infantile nystagmus

“…Clinical sensitivity is dependent on the age of the patient and whether there is a family history [1,4]. Previous data suggest that sequence analysis in "idiopathic" familial cases (where two or more members are affected) identified a variant affecting function in 57-100% of cases [1,2,[13][14][15][16][17][18][19]. While in simplex cases this varies between 0-29% [1,2,13,14,20].…”