Genetic linkage studies of a North Carolina macular dystrophy family†
Materials and 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.
Audere, M.; Rutka, K.; Inaskina, I.; Peculis, R.; Sepetiene, S.; Valeina, S.; Lāce, B. Genetic linkage studies of a North Carolina macular dystrophy family. Medicina 2016, 52, 180-186.
Audere M, Rutka K, Inaskina I, Peculis R, Sepetiene S, Valeina S, Lāce B. Genetic linkage studies of a North Carolina macular dystrophy family. Medicina. 2016; 52(3):180-186.Chicago/Turabian Style
Audere, Mareta; Rutka, Katrina; Inaskina, Inna; Peculis, Raitis; Sepetiene, Svetlana; Valeina, Sandra; Lāce, Baiba. 2016. "Genetic linkage studies of a North Carolina macular dystrophy family." Medicina 52, no. 3: 180-186.