Genetic linkage studies of a North Carolina macular dystrophy family

Autor: Inna Inaskina, Katrina Rutka, Raitis Peculis, Svetlana Sepetiene, Mareta Audere, Sandra Valeina, Baiba Lāce
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Proband
Candidate gene
Genetic Linkage
0302 clinical medicine
Medicine
Copy-number variation
Child
Corneal Dystrophies
Hereditary
Medicine(all)
Genetics
Sanger sequencing
lcsh:R5-920
Middle Aged
Macular dystrophy
Pedigree
Child
Preschool
symbols
Chromosomes
Human
Pair 5
Female
lcsh:Medicine (General)
Tomography
Optical Coherence
Adult
Genetic Markers
Adolescent
DNA Copy Number Variations
Locus (genetics)
03 medical and health sciences
symbols.namesake
Genetic linkage
North Carolina macular dystrophy
Drusen
Parafoveolar hemorrh age
Genome-wide microarray analysis
Humans
Homeodomain Proteins
business.industry
Sequence Analysis
DNA
Latvia
Minor allele frequency
030104 developmental biology
Genetic Loci
Parafoveolar hemorrhage
Automotive Engineering
030221 ophthalmology & optometry
business
Transcription Factors
Zdroj: Medicina
Volume 52
Issue 3
Pages 180-186
Medicina, Vol 52, Iss 3, Pp 180-186 (2016)
Medicina; Volume 52; Issue 3; Pages: 180-186
ISSN: 1010-660X
DOI: 10.1016/j.medici.2016.04.001
Popis: Background and 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. 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.
Databáze: OpenAIRE
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