Description
The p.P86L pathogenic mutation (also known as c.257C>T), located in coding exon 3 of the IDS gene, results from a C to T substitution at nucleotide position 257. The proline at codon 86 is replaced by leucine, an amino acid with a few similar properties. This mutation has been detected in several individuals with Mucopolysaccharidosis type II (MPS II; also called Hunter syndrome) (Popowska E, et al. Hum. Mutat. 1995;5(1):97-100; Vafiadaki E, et al. Arch. Dis. Child. 1998 79(3):237-41; Isogai K, et al. J. Inherit. Metab. Dis. 1998;21(1):60-70; Lampe C et al. JIMD Rep, 2014 Mar;14:99-113; Kosuga M et al. Mol. Genet. Metab., 2016 07;118:190-7), and occurred de novo in at least one individual (Chiong MA et al. Orphanet J Rare Dis, 2017 01;12:7). In addition, several functional studies have shown that this mutation disrupts splicing, resulting in a truncated mRNA product which causes a decrease in IDS enzymatic activity and lysosomal formation (Isogai K, et al. J. Inherit. Metab. Dis. 1998;21(1):60-70; Sukegawa-Hayasaka K, et al. J. Inherit. Metab. Dis. 2006 Dec; 29(6):755-61; Matos L et al. Biochim. Biophys. Acta, 2015 Dec;1852:2712-21; Millat G et al. Biochim. Biophys. Acta, 1998 Mar;1406:214-8). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |