PMC:4596894 / 23544-25523 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4596894","sourcedb":"PMC","sourceid":"4596894","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4596894","text":"Because standard biochemical screening of blood for evidence of a peroxisomal disorder would not have provided a diagnosis in the individuals with HS, our study used a genomic approach to diagnose a rare inborn error of metabolism. Our findings could also be relevant for the development of future therapy for PBDs, because they indicate that partial restoration of the function of altered PEX proteins would lead to a phenotype consistent with HS. Notably, the normal intellectual development and lack of severe hepatic and neurological impairment should be instructive in the expected outcomes of future therapeutic trials. Because of the SNHL and retinal pigmentation, HS is also an important differential diagnosis for Usher syndrome (MIM: 276900). Our study allows precise molecular differentiation of the two diagnoses and indicates that all individuals with SNHL and retinal pigmentation are candidates for mutation analysis of PEX genes. Our data indicate that HS is a clinically and genetically heterogeneous condition due to biallelic variants in PEX1 or PEX6. We did not identify PEX variants in families 7 or 8, nor did we find another genetic cause. However, there are phenotypic differences between these families and those in whom PEX1 or PEX6 variants were identified. Although amelogenesis imperfecta was present in all affected individuals in families 7 and 8, the SNHL in the individuals in family 7 was less severe than in the other affected individuals. In the previously reported affected individual in family 8, the SNHL was unilateral, whereas it was bilateral in all the other affected individuals. In addition, only individual F8-II:1 presented with subtle Beau’s lines, individuals in family 7 did not show any nail abnormalities, and ocular features were not present in any of the individuals in families 7 or 8. So, these phenotypic differences might account for the lack of PEX1 or PEX6 mutations, indicating both clinical and genetic heterogeneity.","tracks":[]}