title: Refinement of the X-linked nonsyndromic high-grade myopia locus MYP1 on Xq28 and exclusion of 13 known positional candidate genes by direct sequencing.
abstract: OBJECTIVE
  Myopia is a common vision problem affecting almost one third of the world's population. It can occur as an isolated genetic condition or be associated with other anomalies and/or syndromes. Seventeen myopia loci have been identified on various chromosomes; however, no specific gene mutations have yet been identified.
  
  
  METHODS
  Two large multigeneration Asian Indian pedigrees (UR006 and UR077) with isolated, nonsyndromic myopia were studied, in which the condition appeared to segregate as an X-linked recessive trait (MYP1; MIM 310460). The degree of myopia was variable in both families, ranging from -6 to -23 D (mean, -8.48 D) with the majority >7.0 D. To map the myopia locus in these families, polymorphic microsatellite markers covering the entire X chromosome were used in linkage analyses performed on 42 genomic DNA samples (13 affected and 29 normal) from both families.
  
  
  RESULTS
  Marker DXYS154, which is located within the pseudoautosomal region in distal Xq28 (PAR2; pseudoautosomal region 2), gave a combined maximum LOD score of 5.3 at = 0 under an autosomal recessive model. Other markers in the region (near but not within the PAR2 region) that showed no recombination with the phenotype in both the families included DXS1108, DXS8087, and F8i13.
  
  
  CONCLUSIONS
  Observation of recombination in family UR006 refined the disease locus to a ∼1.25-Mb region flanked by the proximal marker DXS1073 and distal marker DXYS154. Mutation search in exons and splice junctions of candidate genes CTAG2, GAB3, MPP1, F8Bver, FUNDC2, VBP1, RAB39B, CLIC2, TMLHE, SYBL, IL9R, SPRY3, and CXYorf1 did not detect a pathogenic or predisposing variant.
authors.affiliation: Department of Pharmacology, Creighton University, Omaha, Nebraska, USA.
authors.forename: Uppala
authors.initials: U
authors.lastname: Ratnamala
authors.forename: Robert
authors.initials: R
authors.lastname: Lyle
authors.forename: Rakesh
authors.initials: R
authors.lastname: Rawal
authors.forename: Raminder
authors.initials: R
authors.lastname: Singh
authors.forename: Satti
authors.initials: S
authors.lastname: Vishnupriya
authors.forename: Pamini
authors.initials: P
authors.lastname: Himabindu
authors.forename: Vittal
authors.initials: V
authors.lastname: Rao
authors.forename: Somesh
authors.initials: S
authors.lastname: Aggarwal
authors.forename: Prasuna
authors.initials: P
authors.lastname: Paluru
authors.forename: Lucia
authors.initials: L
authors.lastname: Bartoloni
authors.forename: Terri L
authors.initials: TL
authors.lastname: Young
authors.forename: Ariane
authors.initials: A
authors.lastname: Paoloni-Giacobino
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morris
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Nath
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: Uppala
authors.initials: U
authors.lastname: Radhakrishna
mesh_terms: D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D041321:Chromosomes, Human, X / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005799:Genes, Dominant / Q000235:genetics*; D056726:Genetic Association Studies / Q000379:methods*; D040181:Genetic Diseases, X-Linked / Q000175:diagnosis / Q000235:genetics*; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D007194:India / Q000453:epidemiology; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D009216:Myopia / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree