title: Genetic linkage studies of a North Carolina macular dystrophy family.
abstract: OBJECTIVE
  North Carolina macular dystrophy (NCMD) is a very rare autosomal dominant hereditary disease. Up to date there are three types of NCMD described and consequently named macular dystrophy, retinal: MCDR1, MCDR2 and MCDR3. The aim of this study was to perform linkage and copy number variation analysis for the family affected by NCMD followed by the selected candidate gene sequencing.
  
  
  METHODS
  This study concerned a 3-generation, non-consanguineous Latvian family with NCMD. Genome-wide scan, copy number variation and non-parametric linkage analysis was performed. Analysis resolved the locus of interest to the 5p15.33 region. Two of the genes, iroquois homeobox 2 (IRX2) and iroquois homeobox 4 (IRX4), were selected and sanger sequencing was performed.
  
  
  RESULTS
  Linkage analysis indicated a region on chromosome 5 for the analyzed family, corresponding to a genetic locus previously described for MCDR3 (5p15-p13). Chromosomal aberrations were not identified in the affected family members. An upstream intron variant (NM_001278634: c.-139G > A (rs6876836)) in IRX4 gene segregated with NCMD phenotype in the analyzed family.
  
  
  CONCLUSIONS
  It is unlikely to be the causative mutation of NCMD due to its high minor allele frequency 0.3532. Therefore, the role of IRX2 and IRX4 genes in the pathogenesis of NCMD has not been proved. Considerable variability in visual acuity between individuals of the same age group in all the families examined was noted. No overlap between NCMD grade and family generation was seen in the family described in the present study.
authors: Latvian Biomedical Research and Study Center, Riga, Latvia. Electronic address: mareta.audere@gmail.com.
authors: Mareta
authors: M
authors: Audere
authors: Latvian Biomedical Research and Study Center, Riga, Latvia. Electronic address: katrina.rutka@gmail.com.
authors: Katrina
authors: K
authors: Rutka
authors: Latvian Biomedical Research and Study Center, Riga, Latvia. Electronic address: inna@biomed.lu.lv.
authors: Inna
authors: I
authors: Inaskina
authors: Latvian Biomedical Research and Study Center, Riga, Latvia. Electronic address: raitis@biomed.lu.lv.
authors: Raitis
authors: R
authors: Peculis
authors: Ophthalmology Clinic, Pauls Stradins Clinical University Hospital, Riga, Latvia. Electronic address: dr.sepetiene@gmail.com.
authors: Svetlana
authors: S
authors: Sepetiene
authors: Vision Center, Children's Clinical University Hospital, Riga, Latvia. Electronic address: sandrav@latnet.lv.
authors: Sandra
authors: S
authors: Valeina
authors: Latvian Biomedical Research and Study Center, Riga, Latvia; Centre Hospitalier De l'Université Laval, Québec, Canada. Electronic address: baiba.lace@biomed.lu.lv.
authors: Baiba
authors: B
authors: Lāce
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D003317:Corneal Dystrophies, Hereditary / Q000000981:diagnostic imaging / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D008040:Genetic Linkage; D056426:Genetic Loci; D005819:Genetic Markers; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007844:Latvia; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017422:Sequence Analysis, DNA; D041623:Tomography, Optical Coherence; D014157:Transcription Factors / Q000235:genetics
chemical_list: D005819:Genetic Markers; D018398:Homeodomain Proteins; C501595:IRX2 protein, human; C485533:IRX4 protein, human; D014157:Transcription Factors
keywords: Drusen; Genome-wide microarray analysis; North Carolina macular dystrophy; Parafoveolar hemorrhage; Proband