TABLE 1.
Human imprinting disorder-related diseases.
| Genomic location | Imprinted cluster/lncRNA | Imprinting disorder diseases | Clinical syndromes | Molecular mechanisms | Prevalence in population | References |
| Chromosome 15q11-13 | SNUPF-SNRPN/UBE3A (imprinted lncRNA: UBE3A-ATS) | Prader–Willi syndrome (PWS) (OMIM #176270) | Obesity, reduced muscle tone, diminished swallowing and suckling, infantile hypotonia and hypogonadism, intellectual disability | Deletion the imprinted loci on the paternal allele (70–75%); Maternal UPD of chromosome 15 (20–25%); Epimutations of the DNA methylation at ICR 2%); Small deletions within the ICR (<0.5%) | 1/25.000–1/10.000 | Buiting et al. (1995), Buiting (2010), Fontana et al. (2017), Elbracht et al. (2020) |
| Angelman syndrome (AS) (OMIM #105830) | Developmental delay, intellectual disability, absence of speech, microcephaly, seizures, specific excitable demeanor | Deletion of 15q.11–13 region on the maternal chromosome (70–75%); Point mutation in UBE3A gene (10%); Paternal UPD (3–7%); SNURF ICR loss of methylation (2–3%) | 1/20.000–1/12.000 | Buiting (2010), Eggermann et al. (2015), Elbracht et al. (2020) | ||
| Chromosome 11p-15.5 | H19/IGF2; KCNQ1OT1 (Imprinted lncRNA: H19) H19/IGF2 | Beckwith–Wiedeman syndrome (BWS) (OMIM #130650) | Neonatal macrosomia, postnatal overgrowth, placental mesenchymal dysplasia, Tendency to embryonal tumors, cancer predisposition | Paternal UPD of chromosome 11p15.5 (20% to 25%); KCNQ1OT1-ICR loss of methylation (50%); H19/IGF2-ICR gain of methylation (5%); CDKN1C point mutations (5%); Cluster copy number variation (2–4%) | 1/15.000 | Eggermann et al. (2016), Mussa et al. (2016), Õunap (2016), Kalish et al. (2017) |
| Silver–Russel syndrome (SRS) (OMIM #180860) | Severe intrauterine growth restriction (IUGR), postnatal growth failure with no catch-up, body hemihypoplasia, relative macrocephaly with triangular face, fifth finger clinodactyly and characteristic triangular face, lower birth weight | Loss of methylation at ICR on the paternal allele (40–60%); Maternal UPD of chromosome 7 (5–10%) | 1/100.000–1/75.000 | Cytrynbaum et al. (2016), Eggermann et al. (2016), Õunap (2016), Wakeling et al. (2017) | ||
| Chromo-some 14q32.2 | MEG3/DLK1 (Imprinted lncRNA: MEG3) | Kagami–Ogata syndrome (KOS14) (OMIM #608149) | Polyhydramnios, placentomegaly, poor sucking and hypoventilation in the neonatal period, abdominal wall defects, a distinctive facial appearance, small bell-shaped thorax, coat-hanger ribs | Paternal UPD (65%); Microdeletion affecting the maternal 14q32.2 imprinted region (20%); Hypermethylation of the ICR (15%) | <1 in 1,000,000 | Beygo et al. (2015), Kagami et al. (2015), Ogata and Kagami (2016), Prasasya et al. (2020) |
| Temple syndrome (TS14) (OMIM #616222) | IUGR, PNGR (postnatal growth restriction), hypotonia and motor delay, feeding difficulties in infancy, truncal obesity, scoliosis, precocious puberty, small feet and hands | MEG/DLK1 ICR loss of methylation (61%); Maternal UPD (29%); Deletion in imprinted region (10%) | <1 in 1,000,000 | Ioannides et al. (2014), Gillessen-Kaesbach et al. (2018), Prasasya et al. (2020) |