Uniparentale Disomien : Entstehungsmechanismen und ihre Bedeutung für die klinische Genetik (CME Weiterbildung · Zertifizierte Fortbildung)

Uniparental disomy (UPD) describes a chromosome aberration with the inheritance of both homologues/both copies of a chromosomal segment (heterodisomy) or two copies of one homologue/one chromosomal segment originating from one parent only. Whole chromosome UPDs can be distinguished from segmental and complex UPDs. UPD-associated problems include trisomy mosaicism, homozygosity of autosomal recessively inherited mutations, father-child and mother-daughter transmission of X-chromosomally inherited mutations and genomic imprinting disorders. Genomic imprinting describes the parent of origin-dependent monoallelic expression of some genes. Well-known imprinting disorders include transient neonatal diabetes mellitus, Silver-Russell syndrome, Beckwith-Wiedemann syndrome, upd(14)mat (Temple syndrome), upd(14)pat, Prader-Willi syndrome, and Angelman syndrome. Mechanisms of UPD formation include trisomic and monosomic rescue, gamete complementation, and postfertilization error. Incidence and prevalence for any UPD are not known, but for some imprinting disorder-associated syndromes frequencies up to 1: 3400 have been calculated. The most frequently applied techniques in routine diagnosis are microsatellite marker analysis, methylation-sensitive polymerase chain reaction (PCR), and methylation-specific multiplex ligation-dependent probe amplification (MLPA).