title: A Founder Mutation in MYO7A Underlies a Significant Proportion of Usher Syndrome in Indigenous South Africans: Implications for the African Diaspora.
abstract: OBJECTIVE
  Research over the past 25 years at the University of Cape Town has led to the identification of causative mutations in 17% of the 1416 families in the Retinal Degenerative Diseases (RDD) biorepository in South Africa. A low rate of mutation detection has been observed in patients of indigenous African origin, hinting at novel genes and mutations in this population. Recently, however, data from our translational research program showed two unrelated indigenous African families with Usher syndrome (USH), with the same homozygous MYO7A mutation. Therefore, the extent to which this mutation contributes toward the disease burden in South Africa was investigated.
  
  
  METHODS
  Cohorts of unrelated indigenous South African probands with different RDD diagnoses were tested for the MYO7A c.6377delC mutation. Familial cosegregation analysis was performed for homozygous probands, clinical data were evaluated, and SNP haplotypes were analyzed.
  
  
  RESULTS
  This homozygous MYO7A mutation underlies a remarkable 43% of indigenous African USH cases investigated in this study, the majority of which (60%) were diagnosed clinically with Type 2 USH. All homozygotes shared a common haplotype. This mutation does not appear to cause nonsyndromic vision loss.
  
  
  CONCLUSIONS
  Of interest is the origin of this common mutation relevant to the Bantu population migration into southern Africa. Further investigation of the phenotype may elucidate the disease biology, and perhaps reveal a larger cohort with the same mutation, with which to assess the impact of environmental and genetic modifiers and evaluate therapeutic trials.
authors.forename: Lisa
authors.initials: L
authors.lastname: Roberts
authors.forename: Siddiqah
authors.initials: S
authors.lastname: George
authors.forename: Jacquie
authors.initials: J
authors.lastname: Greenberg
authors.forename: Raj S
authors.initials: RS
authors.lastname: Ramesar
mesh_terms: D000483:Alleles; D044383:Black People / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006720:Homozygote; D063426:Human Migration; D006801:Humans; D008297:Male; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics*; D013019:South Africa / Q000453:epidemiology; D052245:Usher Syndromes / Q000235:genetics*
chemical_list: C000631455:MYO7A protein, human; D000081412:Myosin VIIa; D009218:Myosins