Phenylalanine hydroxylase deficiency exhibits mutation heterogeneity in two large old order Amish settlements

Das Deutsch Center (DDC) Clinic for Special Needs Children, Middlefield, Ohio 44062, USA.
American Journal of Medical Genetics Part A (Impact Factor: 2.16). 08/2007; 143A(16):1938-40. DOI: 10.1002/ajmg.a.31852
Source: PubMed

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    • "One of the known pitfalls of homozygosity mapping is allelic heterogeneity, meaning that there are multiple deleterious variants of the same gene in the population and hence affected individuals may be compound heterozygotes for two mutations (Miano et al. 2000). Indeed, allelic heterogeneity has been documented for at least two disorders prevalent in the OOA: phenylalanine hydroxylase deficiency (Wang et al. 2007) and Cohen syndrome (Taban et al. 2007); in the case of Cohen syndrome, there are affected OOA individuals who are compound heterozygotes for two mutations of the causative gene, VPS13B (Taban et al. 2007). If one wants to avoid the allelic heterogeneity pitfall, one can use Ped- Hunter (Agarwala et al. 1998; Lee et al. 2010) to automatically and systematically extract from AGDB (Agarwala et al. 2003) pedigrees that connect all the obligate carriers and affected individuals. "
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