PMC:4385177 / 11755-13142 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/4385177","sourcedb":"PMC","sourceid":"4385177","source_url":"https://www.ncbi.nlm.nih.gov/pmc/4385177","text":"In order to reduce consumption of DNA and protect this valuable clinical resource for future use, we adopted a two-phased screening strategy. In the first phase, we aimed to identify the most likely candidate genes by sequencing only the exons in which the potentially causal variants were identified in the index family in an independent cohort of 150 subjects with young-onset (\u003c30 years of age), non-autosomal-dominant dystonia of any distribution (younger age of onset was prioritized). In addition, we included a DNA sample from an affected member of the DYT17 kindred. We did not detect any further potentially causal variants in exon 7 of LAPTM5. In exon 2 of HPCA, however, we detected a second, heterozygous, missense variant (c.212C\u003eA) resulting in an amino acid substitution (p.Thr71Asn) at a position just 4 amino acids before the location of the original homozygous variant found in the index family. The affected nucleotide shows extremely high conservation scores (PhyloP = 5.76 [max = 6]; PhastCons = 1 [max = 1]), and the affected amino acid is conserved in all species. Although this amino acid is not recognized as an obligatory Ca2+ coordinator itself, it is still within the second EF-hand domain of hippocalcin (amino acids 60–95 according to UniProt) and is predicted to be damaging, with near maximal probability scores, by all four in silico prediction programs.","tracks":[]}