B-219 Pseudo-exclusion From Paternity due to Maternal Uniparental Disomy of Chromosome 2

Abstract

Abstract Background Uniparental disomy (UPD) is the abnormal situation in which both members of a chromosome pair exclusively comprise material of one of the parents. The incidence of uniparental disomy (UPD) of any chromosome is estimated in 1:3500 live births; this rare condition may be relevant not only for medical genetics, but also for parental testing. Methods We describe a case of trio paternity test using 55 informative STR loci, 30 of these were performed whith GlobalFiler Express KIT - Thermo Fisher (GFE) and Investigator HDPlex - Qiagen (IHDP); capillary electrophoresis using 3500XL - Applied BioSystems; analyses using Genemapper IDX 4.0 - Applied BioSystems. The Y haplotype and 8 additional autosomal STRs were performed by a reference laboratory, which assists us in complex cases. Genotyping with a 1,6 million marker SNP-array (GDA-cyto, Illumina) was analyzed using NxClinical software(Bionano). Results Inconsistencies were observed in four loci, namely TPOX, D2S441, D2S1338 and D2S1360. All four markers mapped on chromosome 2 and were compatible with the mother´s genotype, raising the suspicion of a maternal UPD2. SNP-array analyse showed 4 large blocks with absence of heterozygosity on chromosome 2 (AOH - arr[GRCh38] 2p25.3p24.1(10587_22202427)x2 hmz, 2p21p11.2(43674352_90357502)x2 hmz, 2q22.1q31.1(141240699_170583494)x2 hmz, 2q36.3q37.3(227133255_242119896)x2 hmz), comprising a total of 112,9 Mb. No large AOH blocks were observed in any other chromosome. Conclusions The results indicate the presence of a UPD2. As the result of an unusually high-number of crossing-overs (n=6), several heterozygous and homozygous blocks were present on chromosome 2 (see figure 1). Rare cases of pseudo-exclusions of either maternity or paternity due to UPD have been reported. Together with the case reported here, they highlight the necessity to consider inconsistencies of markers that map into a single chromosome as likely resulting from UPD.