title: Identification of MFRP Mutations in Chinese Families with High Hyperopia.
abstract: OBJECTIVE
  Mutations in MFRP have been reported to cause autosomal recessive posterior microphthalmia, nanophthalmos, and an ophthalmic syndrome characterized by posterior microphthalmia, high hyperopia, retinitis pigmentosa, foveoschisis, and optic disc drusen. High hyperopia is a consistent sign of this syndrome. The purpose of this study was to detect MFRP mutations in 46 unrelated Chinese probands with high hyperopia.
  
  
  METHODS
  Clinical data and genomic DNA were collected from 46 Chinese probands diagnosed as having high hyperopia. Genomic DNA from 42 probands was initially analyzed by whole exome sequencing. MFRP variants were confirmed by Sanger sequencing. The coding sequence of MFRP for four additional probands was also analyzed by Sanger sequencing. Candidate MFRP variants were further validated in available family members and 192 normal individuals.
  
  
  RESULTS
  Potential pathogenic compound heterozygous mutations, including c.287_291del (p.P96Lfs*6), c.1615C>T (p.R539C), c.664C>A (p.P222T), c.1150dup (p.H384Pfs*8), and c.1549C>T (p.R517W), were detected in three of the 46 probands included in this study. The clinical data revealed that all patients in this study had high hyperopia of +13.50D or higher and an eye axial length of 16.78 mm or less. Electroretinography showed normal responses in a patient with missense mutations and reduced rod responses in another patient with missense and truncation mutations in whom optical coherence tomography showed developmental cystoid macular degeneration in both eyes.
  
  
  CONCLUSIONS
  The current study expands our knowledge of the mutation spectrum of MFRP and its associated phenotypes. To our knowledge, this is the first report of MFRP mutations in a Chinese cohort.
authors.affiliation: *BS †MS ‡MD §MD, PhD State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China (YX, XX, SL, XJ, XG, ZY, QZ); and BGI-Shenzhen, Shenzhen, China (LG, JZ, HJ, YY).
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.forename: Liping
authors.initials: L
authors.lastname: Guan
authors.forename: Xueshan
authors.initials: X
authors.lastname: Xiao
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Jia
authors.forename: Ye
authors.initials: Y
authors.lastname: Yin
authors.forename: Xiangming
authors.initials: X
authors.lastname: Guo
authors.forename: Zhikuan
authors.initials: Z
authors.lastname: Yang
authors.forename: Qingjiong
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D004596:Electroretinography; D059472:Exome / Q000235:genetics; D015785:Eye Diseases, Hereditary / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D006956:Hyperopia / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020125:Mutation, Missense; D010375:Pedigree; D017422:Sequence Analysis, DNA; D041623:Tomography, Optical Coherence; D000099274:Frizzled-Related Proteins
chemical_list: D008565:Membrane Proteins; C490110:MFRP protein, human; D000099274:Frizzled-Related Proteins