False deletion of the D15S986 maternal allele in a suspected case of Angelman syndrome

Abstract

BackgroundAngelman syndrome (AS) is a neurological disorder caused by genetic defects of the chromosome region 15q11-q13; some 70–80% of cases are due to deletions of the maternal allele, as the paternal copy is imprinted. Design and methodsA maternal deletion at D15S986 was reported in a suspected case of AS; this marker is located in intron 2 of the ATP10C gene, which has been implicated in the development of AS. A segment of ~830bp, including this marker and the primers used in routine genetic test, was cloned and sequenced. ResultsA single nucleotide deletion (named ATP10C*c.760+3808delA, GenBank accession number HQ856823) was detected in the middle of the forward primer, leading to allele dropout. A large European population sample (N=363) was typed, and the detected variant was characterized as a novel polymorphism, with allele frequencies of 0.882 (TAT allele) and 0.118 (T-T allele). ConclusionsAn alternative primer set was developed, for which the segregation pattern of D15S986 in the proband extended family was normal. It can replace the currently used set.