Allelic heterogeneity in inbred populations: the Saudi experience with Alström syndrome as an illustrative example

Am J Med Genet A. 2009 Feb 15;149A(4):662-5. doi: 10.1002/ajmg.a.32753.


The increased frequency of rare autosomal recessive conditions in genetically isolated populations is a well-established phenomenon. This genetic isolation is invoked as an explanation when one particular mutation is the sole or most frequent mutation observed in a given population and is referred to as the founder effect. This trend of allelic homogeneity is contrasted by an opposite trend when the consanguinity factor is in play. Independent of endogamy at the population level, a consanguineous union is sufficient to render homozygous a percentage of the genome that is directly correlated with the degree of consanguinity. Assuming the gene in question has a normal mutation rate, the resulting homozygosity will inevitably include different defective alleles of that gene. By reporting four novel alleles, we use Alström disease to exemplify the interesting observation of allelic heterogeneity for a very rare autosomal recessive disorder in a highly inbred population. While we frequently assume founder effect in inbred populations, this report should serve to remind us of the powerful effect of the consanguinity factor, a common confounding variable among some of those populations.

Publication types

  • Case Reports

MeSH terms

  • Alleles
  • Base Sequence
  • Cardiomyopathy, Dilated / genetics*
  • Cell Cycle Proteins
  • Child
  • Child, Preschool
  • Codon, Nonsense
  • Consanguinity*
  • DNA / genetics
  • DNA Mutational Analysis
  • Female
  • Frameshift Mutation
  • Hearing Loss, Sensorineural / genetics
  • Heterozygote
  • Homozygote
  • Humans
  • Insulin Resistance / genetics
  • Liver Failure / genetics
  • Male
  • Mutation*
  • Obesity / genetics*
  • Proteins / genetics*
  • Renal Insufficiency / genetics
  • Retinitis Pigmentosa / genetics*
  • Saudi Arabia
  • Syndrome


  • ALMS1 protein, human
  • Cell Cycle Proteins
  • Codon, Nonsense
  • Proteins
  • DNA