Evaluation of MFRP as a candidate gene for high hyperopia.
OBJECTIVE
Mutations in the membrane-type frizzled-related protein (MFRP) gene have been identified in patients with pathologic high hyperopia associated with nanophthalmos or microphthalmia. This study is to test if a mutation in MFRP is responsible for physiologic high hyperopia.


METHODS
DNA was prepared from venous leukocytes of 51 patients with physiologic high hyperopia (refraction of spherical equivalent > or = +5.00 [diopters] D) and 96 controls (refraction of spherical equivalent between -0.50 D and +1.00 D). The coding regions and adjacent intronic sequence of MFRP were amplified by polymerase chain reaction (PCR) and were then analyzed by cycle sequencing. Variations detected were further evaluated in normal controls and available family members by heteroduplex- single-strand conformation polymorphism (SSCP) analysis or sequencing.


RESULTS
The average spherical refractive error of patients was +8.41 D in the right eye (from +6.00 D to +16.5 D) and was +8.76 D in the left eye (from +6.00 D to +16.5 D). Five novel heterozygous variations in MFRP, c.55-14_55-13insGTAT, c.496C>G, c.664C>A, c.669G>A, and c.770G>A, were identified. Of these, c.664C>A (p.Pro222Thr) and c.669G>A (p.=) were not observed in the 96 normal controls. In addition, one known c.192C>G substitution and five single nucleotide polymorphisms (SNPs; rs883247, rs3814762, rs36015759, rs2510143, and rs35885438) were detected.


CONCLUSIONS
Several novel variations in MFRP were detected in Chinese. Our results imply that MFRP is less likely to play a major role in physiologic high hyperopia.
Wang
Panfeng
P
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China.
Yang
Zhikuan
Z
Li
Shiqiang
S
Xiao
Xueshan
X
Guo
Xiangming
X
Zhang
Qingjiong
Q
D001483:Base Sequence; D006801:Humans; D006956:Hyperopia / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D018807:Polymorphism, Single-Stranded Conformational; D000099274:Frizzled-Related Proteins
D008565:Membrane Proteins; C490110:MFRP protein, human; D000099274:Frizzled-Related Proteins