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Table 1 Overview on the molecular findings in the currently known IDs and their clinical characteristics

From: Imprinting disorders: a group of congenital disorders with overlapping patterns of molecular changes affecting imprinted loci

Imprinting disorder Prevalence OMIM Chromosomes/imprinted regions Type of mutation/epimutation and their frequencies MLID Mosaicism Recurrence risk Main clinical features
Transient Neonatal Diabetes Mellitus (TNDM) 1/300.000 601410 6q24: PLAGL1: alt-TSS upd(6)pat 40 %    <1 % IUGR, transient diabetes, hyperglycemia without ketoacidosis, macroglossia, omphalocele
paternal duplications 40 %   No Up to 50 %
methylation defects 20 % ~50 % Yes <1 %
Upd(6)mat Unknown   Chromosome 6, 6q16.1qter upd(6)mat    Yes Unknown  
Silver-Russell syndrome (SRS; Russell-Silver Syndrome, RSS) 1/75.000-1/100.000 180860 7 upd(7)mat ~10 % 1 casea No <1 % IUGR/PNGR, small prematurely calcified placenta, rel. macrocephaly at birth, hemihypotrophy, prominent forehead, triangular face, feeding difficulties
11p15: upd(11p15)mat single case   Unknown Rare
  Genome-wide uniparental diploidy single case   Yes Rare
  maternal duplication <1 %   No Up to 50 %
H19/IGF2: IG DMR hypomethylation >38 %a 7-10 % Yes <1 %
CDKN1C point mutations 1 family reported   No In familial cases: up to 50 % in case of maternal transmission
IGF2 point mutations 1 family reported   No  
Beckwith-Wiedemann syndrome (BWS; Wiedemann-Beckwith syndrome, EMG) 1/15.000 130650 11p15: upd(11p15)pat ~20 %   Yes <1 % Pre- and postnatal overgrowth, organomegaly, macroglossia, omphalocele, neonatal hypoglycemia, hemihypertrophy, increased tumour risk
  Genome-wide uniparental diploidy ~2 %   Yes <1 %
  chromosomal aberrations 2-4 %   No Up to 50 %
IH19/IGF2: IG DMR; KCNQ1OT1: TSS-DMR hypermethylation 5-10 %   Yes unclear
  hypomethylation 40-50 % 25 % Yes <1 %
CDKN1C point mutations 5 % (sporadic) 40–50 % (families)   No Up to 50 %
Kagami-Ogata syndrome (KOS14; upd(14)pat syndrome) unknown 608149 14q32: upd(14)pat 65 %    in case of RT IUGR, polyhydramnion, abdominal and thoracal wall defects, bell-shaped thorax, coat-hanger ribs
MEG3/DLK1: IG DMR maternal deletion 15 % up to 50 %
MEG3: TSS DMR aberrant methylation 20 % <1 %
Temple syndrome (TS14; upd(14)mat syndrome) unknown 616222 14q32: upd(14)mat 78 %    In case of RT IUGR/PNGR, neonatal hypotonia, feeding difficulties in infancy, truncal obesity, scoliosis, precocious puberty, small feed and hands
MEG3/DLK1: IG DMR paternal deletion 10 %   Up to 50 %
MEG3: TSS DMR aberrant methylation 12 % 1 casea <1 %
Prader-Willi syndrome (PWS) 1/25.000-1/10.000 176270 15q11-q13 paternal deletion 70 %    Up to 50 % PNGR, mental retardation, neonatal hypotonia, hypogenitalism, hypopigmentation, obesity/hyperphagia
upd(15)mat <30 %   In case of RT
aberrant methylation ~1 % 1 case <1 %
Angelman syndrome (AS) 1/20.000-1/12.000 105830 15q11-q13: maternal deletion 70 %   No Up to 50 % mental retardation, microcephaly, no speech, unmotivated laughing, ataxia, seizures, scoliosis
  upd(15)pat 1-3 %    In case of RT
  aberrant methylation ~4 %   Yes <1 %
UBE3A point mutations 10-15 %   No In familial cases: up to 50 % in case of maternal transmission
Precocious puberty (central precocious puberty 2; cppb2) Unknown 614356 15q11.2: MKRN3 point mutations 100 %   No In familial cases: up to 50 % in case of paternal transmission Early activation of the hypothalamic-pituitary-gonadal axis results in gonadotropin-dependent precocious puberty
Upd(16)mat Unknown   Chromosome 16 upd(16)mat, often associated with chromosomal aberrations    Yes <1 % IUGR (40-85 %); heterogeneous, but no specific or unique symptoms
Pseudohypo-parathyroidism (PHP1B, PHP1C, PHP1A) unknown 603233 20q13: Maternally inherited deletions causing aberrant methylation 8.5 %    Up to 50 % in case of maternal transmission Resistance to PTH and other hormones; Albright hereditary osteodystrophy, subcutaneous ossifications, feeding behaviour anomalies, abnormal growth patterns
612462 GNAS isolated epimutations 42.5 % 12.5 %   <1 %
103580   upd(20)pat 2.5 % 12.5 %   <1 %
maternal and paternal heterozygous loss of function mutations in GNAS coding sequence 46.5 %   No Up to 50 % in case of maternal transmission
Upd(20)mat syndrome unknown   Chromosome 20 upd(20)mat    No <1 % IUGR, PNGR, feeding difficulties
  1. IUGR intrauterine growth retardation, PNGR postnatal growth retardation
  2. aThis case carries both upd(7)mat and a TS14 epimutation [82], if studied in different tissues