Dataset Information

Sequence variations of GRM6 in patients with high myopia.

ABSTRACT:

Purpose

Mutations in the glutamate receptor metabotropic 6 gene (GRM6) have been identified in patients with congenital stationary night blindness (CSNB1B). High myopia is usually observed in CSNB1B patients. This study tested if any mutations in GRM6 were solely responsible for high myopia.

Methods

DNA was prepared from the venous leukocytes of 96 Chinese patients with high myopia (refraction of spherical equivalent of at least -6.00 diopters [D]) and 96 controls (refraction of spherical equivalent between -0.50 D and +2.00 D with normal visual acuity). The coding regions and adjacent intronic sequence of GRM6 were amplified by a polymerase chain reaction (PCR) and then analyzed by cycle sequencing. Detected variations were evaluated in normal controls by heteroduplex-single-strand-conformation (SSCP) polymorphism analysis or restriction fragment polymorphism (RFLP).

Results

Four novel variations predicted to have potential functional changes were identified: c.67-82delCAGGCGGGCCTGGCGCinsT (p.Gln23_Arg28delinsCys), c.858-5a>g (r.spl?), c.1172G>A (p.Arg391Gln), and c.1537G>A (p.Val513Met). Except for c.1172G>A, the other three were not detected in the 96 controls. In addition, five rare variations-(c.72G>A, c.504+10g>t, c.726-50g>c, c.1359C>T, and c.1383C>T)-and one common variation (c.2437-6g>a) without predicted functional consequences and nine known single nucleotide polymorphisms (SNPs) were also detected.

Conclusion

Three novel variations with potential functional consequences were identified in the GRM6 of patients with high myopia, suggesting a potential role in the development of myopia in rare cases.

SUBMITTER: Xu X

PROVIDER: S-EPMC2765235 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Publications

Sequence variations of GRM6 in patients with high myopia.

Xu Xiaoyu X Li Shiqiang S Xiao Xueshan X Wang Panfeng P Guo Xiangming X Zhang Qingjiong Q

Molecular vision 20091019

<h4>Purpose</h4>Mutations in the glutamate receptor metabotropic 6 gene (GRM6) have been identified in patients with congenital stationary night blindness (CSNB1B). High myopia is usually observed in CSNB1B patients. This study tested if any mutations in GRM6 were solely responsible for high myopia.<h4>Methods</h4>DNA was prepared from the venous leukocytes of 96 Chinese patients with high myopia (refraction of spherical equivalent of at least -6.00 diopters [D]) and 96 controls (refraction of s ...[more]

PMID: 19862333

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Project description: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.

Project description:PurposeTo investigate monthly and seasonal variations in the progression of myopia in children enrolled in the Correction of Myopia Evaluation Trial (COMET).MethodsAn ethnically diverse cohort of 469 myopic 6- to <12 year-old children was randomized to single vision or progressive addition lenses and followed for 3 years with 98.5% retention. Progression of myopia was measured semiannually by noncycloplegic autorefraction (Nidek ARK 700A) and annually by cycloplegic autorefraction, with the former measurements used in these analyses. The semiannual progression rate was calculated as (change in spherical equivalent refraction between two consecutive semiannual visits/number of days between the two visits) times 182.5. Months were categorized as the midpoint between two visit dates. Seasons were classified as winter (October through March) or summer (April through September). The seasonal difference was tested using a linear mixed model adjusting for demographic variables (age, sex, ethnicity), baseline refraction, and treatment group.ResultsData from 358 children (mean [± SD] age = 9.84 ± 1.27 years; mean myopia = -2.54 ± 0.84 diopters [D]) met the criteria for these analyses. Myopia progression varied systematically by month; it was slower in April through September than in the other months. Mean progression in winter was -0.35 ± 0.34 D and in summer was -0.14 ± 0.32 D, a statistically significant difference (0.21 D, P < 0.0001). The same seasonal pattern was found by age, sex, ethnicity (except in the small sample of Asians), lens type, and clinical center.ConclusionsThe slower progression of myopia found in summer is likely related to children's spending more time outdoors and fewer hours in school. The data have clinical implications regarding the time of year and the frequency with which myopic children have eye examinations and the need for precise timing of visits in clinical trials testing new myopia treatments. (ClinicalTrials.gov number, NCT00000113.).

Dataset Information

Sequence variations of GRM6 in patients with high myopia.

Purpose

Methods

Results

Conclusion

Publications

Sequence variations of GRM6 in patients with high myopia.

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