title: Identification of two mutations of the RHO gene in two Chinese families with retinitis pigmentosa: correlation between genotype and phenotype.
abstract: OBJECTIVE
  To describe the clinical and genetic findings in two Chinese families with retinitis pigmentosa (RP).
  
  
  METHODS
  Two unrelated families were examined clinically. After informed consent was obtained, genomic DNA was extracted from the venous blood of all participants. Genotyping and haplotyping analysis was performed on the known genetic loci for autosomal dominant retinitis pigmentosa (adRP) with a panel of polymorphic markers in the two families, and then mutation screening of all coding exons of the RHO gene was performed by direct sequencing of PCR-amplified DNA fragments. Whenever substitutions were identified in a patient, restriction fragment length polymorphism analysis was performed on all available family members and on 100 normal controls.
  
  
  RESULTS
  Clinical examination and pedigree analysis revealed two four-generation families (83 and 112) with adRP. A significant two-point linkage odd disequilibrium (LOD) score was generated at marker D3S1292 (Zmax=1.90, θ=0) for family 83 and (Zmax=2.77, θ=0) for family 112, respectively, and further linkage and haplotype studies confined the disease locus to 3q21-22 where the RHO gene is located. Mutation screening of the RHO gene in the two families revealed a G→C transversion at position 505 (p.A169P) of the cDNA sequence in family 83 and a C→A transversion at position 1040 (p.P347Q) of the cDNA in family 112. The novel p.A169P and recurrent p.P347Q mutations cosegregated with the phenotypes of the two families. Secondary structure prediction suggested that the mutant rhodopsin 169P led to significant secondary structure changes between residues 165 and 169, which may interfere with the correct folding of the transmembrane domain.
  
  
  CONCLUSIONS
  Two mutations of the RHO gene were identified in two Chinese families with adRP. Our findings further suggest codon 347 is the mutation hotspot of the RHO.
authors.affiliation: Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Pan
authors.forename: Tingting
authors.initials: T
authors.lastname: Lu
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zhang
authors.forename: Hanjun
authors.initials: H
authors.lastname: Dai
authors.forename: Weiyu
authors.initials: W
authors.lastname: Yan
authors.forename: Fengge
authors.initials: F
authors.lastname: Bai
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D044466:Asian People; D003062:Codon; D005091:Exons; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D017433:Protein Structure, Secondary; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000473:pathology; D012243:Rhodopsin / Q000235:genetics*
chemical_list: D003062:Codon; D005819:Genetic Markers; D012243:Rhodopsin