Alleles with more than one mutation can complicate genotype/phenotype studies in Mendelian disorders: Lessons from Gaucher disease

Abstract Autosomal resessive Mendelian disorders usually result from two inherited disease-causing mutations. However, this is not always the case. Focusing on Gaucher disease, which results from mutations in GBA1 , we found that more comprehensive genotyping revealed important exceptions. For example, patients with uniparental disomy or new mutations do not inherit a mutation from each parent. Furthermore, we identified patients found to carry more than one GBA1 mutation on the same allele. It is essential to examine the entire GBA1 gene in order to establish an accurate genotype. Missing the second mutation can complicate genotype/phenotype studies and result in improper genetic counseling.