Dataset Information

Common MFRP sequence variants are not associated with moderate to high hyperopia, isolated microphthalmia, and high myopia.

ABSTRACT: The membrane-type frizzled-related protein (MFRP) gene is selectively expressed in the retinal pigment epithelium and ciliary body, and mutations of this gene cause nanophthalmos. The MFRP gene may not be essential for retinal function but has been hypothesized to play a role in ocular axial length regulation. The involvement of the MFRP gene in moderate to high hyperopic, isolated microphthalmic/anophthalmic, and high myopic patients was tested in two phases: a mutation screening/sequence variant discovery phase and a genetic association study phase.Eleven hyperopic, ten microphthalmic/anophthalmic, and seven non-syndromic high-grade myopic patients of varying ages and 11 control subjects participated in the mutation screening phase. Sixteen primer pairs were designed to amplify the 13 exons of the MFRP gene including intron/exon boundaries. Polymerase chain reactions were performed, and amplified products were sequenced using standard techniques. Normal and affected individual DNA sequences were compared alongside the known reference sequence (UCSC genome browser) for the MFRP gene. The genetic association study included 146 multiplex non-syndromic high-grade myopia families. Seventeen intragenic and flanking single nucleotide polymorphisms (SNPs) were chosen for the MFRP gene and genotyped in the large data set using the Taqman allelic discrimination assay. The family-based association Pedigree Disequilibrium Test (PDT) and GenoPDT were performed.The average spherical refractive error of the hyperopic patient cohort was +4.21 diopters (D; range +2.00 to +9.25 D) and of the myopic patient cohort was -12.36 D (range -8.25 to -14.50 D). A total of 16 SNPs were identified by direct sequencing. No significant association was determined between the 16 MFRP gene SNPs and the moderate to high hyperopia, microphthalmia/anophthalmia affection status, and high myopia. Family based association analysis did not reveal any association between the 17 SNPs genotyped in the larger family data set for any refractive error type.Sequence variants of the MFRP gene do not appear to be associated with either the less severe forms of hyperopia, extreme forms of limited eye growth and development, or high myopia. These results indicate that the MFRP gene may not play a role in regulating ocular axial length in these phenotypes.

SUBMITTER: Metlapally R

PROVIDER: S-EPMC2268852 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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Common MFRP sequence variants are not associated with moderate to high hyperopia, isolated microphthalmia, and high myopia.

Metlapally Ravikanth R Li Yi-Ju YJ Tran-Viet Khanh-Nhat KN Bulusu Anuradha A White Tristan R TR Ellis Jaclyn J Kao Daniel D Young Terri L TL

Molecular vision 20080304

<h4>Purpose</h4>The membrane-type frizzled-related protein (MFRP) gene is selectively expressed in the retinal pigment epithelium and ciliary body, and mutations of this gene cause nanophthalmos. The MFRP gene may not be essential for retinal function but has been hypothesized to play a role in ocular axial length regulation. The involvement of the MFRP gene in moderate to high hyperopic, isolated microphthalmic/anophthalmic, and high myopic patients was tested in two phases: a mutation screenin ...[more]

PMID: 18334955

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Project description:PurposeTo investigate the prevalence of myopia in Chinese primary school students and their ocular biometrics including axial length (AL), corneal radius of curvature (CRC) and spherical equivalent refraction (SER). To analyze their association with potential myopia risk factors, such as body mass index (BMI), cram school, time of outdoor activity and electronic screen use.MethodsIn this cross-sectional study of 4500 primary school students from 5 schools, participants underwent refraction using non-cycloplegic autorefractor and visual acuity testing. A follow-up study in the same schools was conducted in 2022. Myopia was defined as SER ≤ -0.50 diopter (D) and uncorrected visual acuity (UCVA) < 0.00 logMAR (6/6). Logistic regression models were used to determine factors associated with myopia.ResultsAfter excluding 389 participants, the overall prevalence of myopia was 33.6%. The prevalence of high myopia was 0.6%. The prevalence of myopia in girls was significantly higher than that in boys (37.6% vs. 30.0%, p < 0.001). The height, weight and BMI were significantly associated with AL (r = 0.471, r = 0.440, r = 0.276, p < 0.001, respectively). AL/CRC ratio was more highly correlated with SER than AL alone. Regression analysis showed that AL/CRC and hyperopia reserve were associated with myopia onset in the subsequent year (F = 201.557, p < 0.001; F = 68.934, p < 0.001). The cut point of hyperopia reserve for myopia in the subsequent year for grade 1 students was + 0.31D. Age (p < 0.001), parental myopia (p = 0.001) and lack of outdoor activity between classes (p = 0.049) were independently associated with higher prevalence rates of myopia.ConclusionThe prevalence of myopia among Chinese schoolchildren is alarming high. Consistent with previous cross-sectional data, AL/CRC and hyperopia reserve could function as myopia detection indicators. The hyperopia reserve among children aged between 6 ~ 7 years was low. Healthcare providers need to raise parents' awareness of the importance of regular eye examination and proper optical correction.

Project description:PURPOSE:Anophthalmia and microphthalmia (A/M) are rare congenital ocular malformations presenting with the absence of eye components or small eyes with or without structural abnormalities. A/M can be isolated or syndromic. The stimulated by retinoic acid gene 6 (STRA6) and Sloan-Kettering viral oncogene homolog (SKI) genes are involved in vitamin A metabolism, and are implicated with A/M developmental abnormalities in human and animal studies. Vitamin A metabolism is vital to normal eye development and growth. This study explores the association of these genes in a cohort of subjects with A/M. METHODS:STRA6 and SKI were screened for sequence variants by direct sequencing of genomic DNA samples from 18 affected subjects with A/M. The DNA samples of 4 external, unrelated controls were initially screened. Eighty-nine additional unrelated controls were screened to confirm that any sequence variants found in the affected subject DNA samples were related to the phenotype. Coding regions, intron-exon boundaries, and untranslated regions were sequenced by standard techniques. Derived DNA sequences were compared to known reference sequences from public genomic databases. RESULTS:For STRA6, a novel coding non-synonymous sequence variant was found in one subject, resulting in an amino acid change from glycine to glutamic acid in residue 217. One novel nonsense sequence variant found in the same subject changed the STRA6 amino acid residue 592 from cytosine to thymine resulting in a premature stop codon. For SKI, a known coding non-synonymous sequence variant (rs28384811) was found in 3 subject DNA samples and 11/89 control DNA samples. Four novel coding-synonymous sequence variants were observed in SKI. CONCLUSIONS:The STRA6 sequence variants reported in this study could play a role in the pathogenesis of A/M by structural changes to the STRA6 protein. We can attribute 4% A/M incidence in this cohort to these sequence variants. Although no SKI sequence variants were found in this cohort, SKI should not be ruled out as a candidate gene for A/M due to the small cohort size.

Dataset Information

Common MFRP sequence variants are not associated with moderate to high hyperopia, isolated microphthalmia, and high myopia.

Publications

Common MFRP sequence variants are not associated with moderate to high hyperopia, isolated microphthalmia, and high myopia.

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