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>6,250 cases included
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How to cite this
database: |
Visitors |
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last update: 16. Dec.
2024 |
Created
by Dr. Thomas Liehr (PhD) |
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New book on uniparental disomy (UPD) and imprinting:
2024 - epubli
available in 2 languages
English German
| AIM OF THIS PAGE | ||||||||||
| PATIENT AND USER INFORMATION | ||||||||||
| Patient organizations | UPD-frequency and number of reported cases |
How to use this page? | ||||||||
| Definition of UPD | First description | Diagnostic testing | ||||||||
| UPD BY CHROMOSOME | ||||||||||
| UPD 1 mat pat unclear |
UPD 2 mat pat unclear |
UPD 3 mat pat unclear |
UPD 4 mat pat unclear |
UPD 5 mat pat unclear |
UPD 6 mat pat unclear |
UPD 7 mat pat unclear |
UPD 8 mat pat unclear |
UPD 9 mat pat unclear |
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| UPD 10 mat pat unclear |
UPD 11 mat pat unclear |
UPD 12 mat pat unclear |
UPD 13 mat pat unclear |
UPD 14 mat pat unclear |
UPD 15 mat pat unclear |
UPD 16 mat pat unclear |
UPD 17 mat pat unclear |
UPD 18 mat pat unclear |
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| UPD 19 mat pat unclear |
UPD 20 mat pat unclear |
UPD 21 mat pat unclear |
UPD 22 mat pat unclear |
UPD X mat pat unclear |
UPD Y mat pat unclear |
UPD XX mat pat unclear |
UPD XY mat pat unclear |
UPD all mat pat unclear |
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| ABOUT IMPRINTING | ||||||||||
| DISCLAIMER | ||||||||||
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links
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1. collect all available case reports on uniparental disomy (UPD) in clinical cases; i.e. UPD in tumor (e.g. {909} and leukemia are not of interest in this page; also not included are acquired but non-cancer-related disorders with UPD (e.g. {738; 1022; 1032; 1323; 1343; 1405; 1441; 1513; 1530; 1533}).
Interstingly also some known inherited syndromes can be acquired as well - i.e. present as mosaic state {299; 1036; all whole genomic UPDs - see link1 , link2 and link3}
2. provide information for patients and clinicians.
The concept of uniparental disomy (UPD) was introduced in 1980 into medical genetics by Eric Engel {456}. In 1987 later Créau-Goldberg et al. {395} described a case with maternal origin of a de novo balanced t(21q;21q) identified by an ets-2 polymorphism, which was the first case of UPD proven by molecular methods.
Uniparental disomy (UPD) is the presence of a chromosome pair derived only from one parent in a disomic cell line. UPD is one form of aberrant origin for disomic cells. Uniparental disomy can involve homozygosity for the chromosome, and the term isodisomy has been suggested for this phenomenon {456; 757}. If uniparental chromosomes are heterozygote this is called heterodisomy.
Isodisomy is important to be distinguished from heterodisomy, as isodisomy can lead to the activation of recessive gene-mutations.
Hetero- and isodisomy can be present in case a disease is present due to an imprinting defect -> see here.
UPD (in some tissues) also may evolve during lifetime and lead to a (non-cancer) disease {1135}; mostly this appears during embryogenesis {1415}; this may also lead to progression during lifetime {549; 555; 580; 581; 915; 1062; 1128; 1154}. Also UPD seems to be frequent as confined placental mosaicism {1076}.
Also there are hints that UPD is more likely to take place in children born by older mothers {584; 550-551}.
Interestingly in leukemia recently telomere shortening was positively correlated to development of UPD {917}!
Extremely rarely UPD may be present in mosaic in the germline {737; 740} and inheritance of UPD within families {235; 284; 741}.
Obvioulsy, if there is a duplication or triplication of genetic material this is / may go together with a UPD - there are some cases tested for this and reported {749; 750}.
Interstingly, acquired UPD was seen as a rescue mechanism to get rid of ring chromosomes in stem celllines {819; 998; 1432}.
UPD changes the methylation profile of the cell {982}.
It was shown that UPD may be acquired during live time - esp. in 4q and 14q {991; 992}.
Interestingly, rarely, reverting UPD may lead to spontaneous remission of diseases {621 =1121; 1120; 1122}.
In 12/39 cases with UPD in any of the imprinted chromosomes (30.8%), skewed X-chromosome inactivation was observed {1176}.
UPD may play a role in brain - as tissue specific UPD {1242}.
Impact and frequency of UPD in in vitro-fertilization is still a matter of discussion {1275}; Ref {1477} suggest there is not impact of IVF on UPD formation.
In {1294} a murine inducible uniparental chromosome disomy (UPD) system is presented.
UPD is associated with trisomic rescue and thus advanced maternal age; acc. to {1555} at least 2/3 of mosaic trisomy cases have biparental inheritance, while 1/3 has UPD. This fits with the biparental division of cell nuclei, as shown in {1556} - which means each cell knows which chromosomes derived from which parent.
In {1436} it is highlighted that UPD is a chromosomic disorder.
Reviews on UPD: see 1228, 1229, 1278
Links for families with a child having a UPD related disorder
all
UPD-related syndromes
General
information on UPD from UNIQUE
UNIQUE = rare
chromosome disorder support group
CONTACT a family - for families with disabled children
LEONA - Verein für Eltern chromosomal geschädigter Kinder e.V. (German site)
Valentin APAC
Unique Danmark
Chromosome Disorder Outreach (CDO)
Living with Trisomy
Network Imprinting defects
contact: bernhard.hosthemke@uni-due.de
Angelman Syndrome
Angelman Syndrome Foundation
ASSERT - Angelman Syndrome Support Education and Research Trust
Dutch Angelman Syndrome Association
The Angelman project
Angelman-Verein
(German)
Beckwith-Wiedemann Syndrome
Associazione Italiana Sindrome di Beckwith-Wiedemann
Beckwith-Wiedemann children foundation
Prader-Willi Syndrome
International Prader-Willi Syndrome Association
Prader-Willi-Syndrome Association (USA)
Prader-Willi-Syndrome Association (UK)
Prader-Willi-Syndrom-Vereinigung (PWSV) Deutschland e.V. (German site)
Prader-Willi-Syndrome in Romania (Romanian site and English translation)
Prader-Willi-Syndrome Assoziation (NZ)
Silver Russel Syndrome
A global
Alliance for Silver-Russel syndrome
The Magic foundation
Human Growth Foundation
Restricted Growth Association
Child Growth Foundation
Silver-Russel-Syndrom
(German)
This page is organized like the 'sister-page' on small supernumerary marker chromosomes (sSMC)-
the structure is explained here.
In 214,915 trios of normal population 105 cases of whole chromosome UPD was found, this is a rate of 1 in 2000 births {1082}. For double UPDs (2 chromosomes at same time) they estimate a frequency of 1 in 50,000 births.
UPD rate in patients with abnormal phenotypes (neurodev. disorders) was 2 in 1000 acc. to {1213}.
In 32,067 parent-child trios (children were index patients with abnormal phenotypes = neurodev. disorders) 99 cases with whole chr. UPD and 13 with segmental UPD were found; i.e. 3 in 1000 {1300}. Patients were pre-studied collective where some UPD cases have been found before by other tests and not included here in this exome based sequencing approach. Isodisomy:heterodisomy:mixed:segmental UPD was 39:15:45:13 {1300}.
Overall they found 199 individuals with UPD (199 single and 6 double UPDs) in 916,712 parent-child duos. There were examples for all chromosomes except for 18 and Y.
Paternal versus maternal UPD was observed at a rate of 1 to 3 {1082}.
The overall 205 cases from Fig. 2 of this study {1082} were not included in this page due to lack of clinical data. However most frequent there was UPD(16)mat, which would support the view, that chromosome 16 does not underly imprinting.
In {1273} UPD(21) was possible to be suggested in 2 out of 116,224 trio exams for paternity testing.
UPD in mentally retarded is ~0.13% {828}, i.e. 14,574 cases were studied for congenital aberrations and/or chromosomal aberrations by SNP-aCGH {828}: 19 cases with complete or segmental iUPD identified; 12 with iUPD(15), 7 with iUPD of other chromosomes and recessive gene activation.
regions of homozygozyty (ROH = potential iUPD) were found in following percentages;
in 6% one or more ROH of >10Mb
- 78% of those suggested to be due not to iUPD
- 22% involving a single chromosome.
in {1559} it is highlighted that phenotypic spectrum of clincal features for UPD cases includes in most of the individuals neurodevelopmental abnormalities and seizures, whil tall stature as well as obesity are not represented.
No increased rates of UPD (examplified in PWS patients) was found after assisted reproduction techniques {918}.
Acc. to {447} 1 UPD case was found in 160 prenatal cases, testing overall 264 chromosomes.
Acc. to {1289} 7 UPD cases were found in 4512 prenatal cases, testing all chromosomes by SNP-array.
UPD as a problem in prenatal care is highlighted here {1427}
Acc. to {1352} 0 UPD cases were found in 6,766 clinical trophectoderm biopsies, testing all chromosomes by NGS-based chromosomal analysis.
12/610 (2%) euploid aborted products of conceptions had iso-UPD of chr. 1, 4, 8, 11, 17, 21, 22 (one each), 6 (2 cases) and 7 (3 cases) - cases not included in this database {1445}.
Among 24,900 aborted products of conceptions there were 196 whole genome UPDs, 13 whole chromosome UPD, 5 with segmental UPD (chr. 11) - cases not included in this database {1446}.
Acc. to {817} 2 iUPDseg cases were found in 268 spontaneous abortion cases.
And acc. to {1500} a GTG banding study (!?) found 1 UPD case among 294 abortion tissues.
Acc. to {163} UPD is found in 0.4% of 2,019 (develop)mentally retarded children studied by genome wide SNP-based array-CGH.
Acc. to {797} UPD is found in 0.56% of 1,075 (develop)mentally retarded children studied by genome wide SNP-based array-CGH in trios - i.e 5 complete and 1 segmental.
Acc. to {815} UPD is found in 0% of 322 (develop)mentally retarded children studied by genome wide SNP-based array-CGH in trios and 11/836 = 1.3% acc to {896}.
UPD 14 was found in 3.6% of 335 balstomeres and normal karyotype, while it was found in 34% of 35 blastomeres studied with constitutional inv(9) {636} and 2/3401 had iso-UPD for all chromosomes and no heterodisomy = 0.06% {999}. Already in 2010 no UPD was found in 50 studied blastomeres {1000}.
Rate of segmental UPD was estimated to be one per 3,806 chromosome pairs (0.026%) {702}
however, in 14/267 (5.2%) mentally impaired patients hints on UPDs of 1-1.5 Mb in size {924}.
Rate of UPD in discarded morphologically abnormal embryos 9/241 - 5 euploid and 4 aneuploid {898}.
In 3/967 trophectoderm biopsies UPD was found in {1131}.
Rate of UPD in miscarriages 9/468 = 1.9% {1042}
Rate of UPD in 651 sonographic abnormal fetuses was 2/651 = 0.3% {899}.
Rate of UPD (no chromosome specified) in obese people 12/1068 {1255}
UPD is reported in offspring of balanced chromosomal rearrangements - in 2019 {1169} found only 1/1747 UPD(14)mat case where one parent had a Robertsonian translocation involving chromosomes 14, or 15; only UPD 14 and 15 were excluded. From that UPD risk in such cases is suggested to be ~0.06%.
In {1577} 1/2151 blastocysts of Robertsonian translocation carriers had a UPD(15)mat.
UPD(mat) to UPD(pat) has a rate of 9:1 acc. to {1319}.
| chr. | no karyotype | normal karyotype |
abnormal balanced karyotype |
abnormal unbalanced karyotype |
sSMC | segmental | all | IN SUMMARY | ||||||||||||||
| chr. | mat | pat | uncl. | mat | pat | uncl. | mat | pat | uncl. | mat | pat | uncl. | mat | pat | uncl. | mat | pat | uncl. | mat | pat | uncl. | all |
| 1 | 24 | 34 | 20 | 9 | 11 | 12 | 0 | 1 | 0 | 4 | 0 | 16 | 2 | 0 | 2 | 6 | 6 | 10 | 45 | 52 | 60 | 157 |
| 2 | 38 | 35 | 10 | 8 | 5 | 14 | 1 | 0 | 0 | 12 | 1 | 8 | 1 | 0 | 0 | 4 | 2 | 6 | 64 | 43 | 38 | 145 |
| 3 | 9 | 4 | 5 | 1 | 2 | 8 | 1 | 0 | 0 | 2 | 1 | 3 | 2 | 0 | 0 | 2 | 0 | 3 | 17 | 7 | 19 | 43 |
| 4 | 16 | 7 | 3 | 3 | 3 | 1 | 2 | 0 | 0 | 3 | 1 | 6 | 1 | 0 | 1 | 7 | 2 | 1 | 32 | 13 | 12 | 57 |
| 5 | 5 | 5 | 4 | 1 | 3 | 3 | 0 | 0 | 0 | 2 | 1 | 3 | 1 | 0 | 0 | 1 | 4 | 2 | 10 | 13 | 12 | 35 |
| 6 | 24 | 108 | 1 | 8 | 13 | 2 | 0 | 0 | 0 | 11 | 5 | 2 | 1 | 2 | 0 | 3 | 7 | 8 | 47 | 135 | 13 | 195 |
| 7 | 447 | 8 | 1 | 35 | 4 | 0 | 7 | 0 | 0 | 8 | 1 | 3 | 9 | 0 | 1 | 16 | 3 | 12 | 522 | 16 | 17 | 555 |
| 8 | 7 | 9 | 8 | 3 | 2 | 6 | 0 | 0 | 0 | 4 | 3 | 7 | 1 | 0 | 2 | 1 | 2 | 4 | 16 | 16 | 27 | 59 |
| 9 | 7 | 5 | 1 | 6 | 0 | 1 | 1 | 0 | 0 | 10 | 5 | 11 | 1 | 1 | 0 | 3 | 0 | 6 | 28 | 11 | 19 | 58 |
| 10 | 6 | 3 | 1 | 1 | 2 | 1 | 0 | 0 | 0 | 2 | 1 | 2 | 1 | 0 | 0 | 1 | 0 | 0 | 11 | 6 | 4 | 21 |
| 11 | 3 | 665 | 2 | 3 | 4 | 1 | 0 | 0 | 0 | 6 | 5 | 1 | 0 | 0 | 0 | 5 | 234 | 10 | 17 | 908 | 14 | 939 |
| 12 | 2 | 3 | 3 | 1 | 1 | 0 | 0 | 0 | 0 | 3 | 0 | 2 | 2 | 0 | 0 | 0 | 0 | 3 | 8 | 4 | 8 | 20 |
| 13 | 6 | 4 | 3 | 1 | 0 | 1 | 3 | 4 | 0 | 5 | 2 | 3 | 0 | 0 | 0 | 5 | 2 | 4 | 20 | 12 | 11 | 43 |
| 14 | 88 | 65 | 1 | 26 | 29 | 11 | 37 | 8 | 0 | 18 | 3 | 2 | 7 | 3 | 0 | 7 | 6 | 12 | 183 | 114 | 26 | 323 |
| 15 | 2116 | 320 | 3 | 246 | 47 | 20 | 27 | 21 | 0 | 39 | 4 | 12 | 28 | 7 | 0 | 3 | 5 | 12 | 2459 | 404 | 47 | 2910 |
| 16 | 51 | 10 | 6 | 9 | 2 | 23 | 0 | 0 | 0 | 73 | 3 | 18 | 2 | 0 | 0 | 2 | 0 | 6 | 137 | 15 | 53 | 205 |
| 17 | 4 | 2 | 0 | 1 | 0 | 2 | 2 | 0 | 0 | 1 | 0 | 4 | 0 | 0 | 0 | 4 | 2 | 7 | 12 | 4 | 13 | 29 |
| 18 | 1 | 3 | 2 | 0 | 2 | 2 | 0 | 0 | 0 | 4 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 3 | 7 | 7 | 8 | 22 |
| 19 | 0 | 3 | 2 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 4 | 6 | 10 |
| 20 | 34 | 19 | 4 | 2 | 1 | 4 | 0 | 0 | 0 | 3 | 1 | 0 | 4 | 1 | 0 | 1 | 9 | 2 | 44 | 31 | 10 | 85 |
| 21 | 6 | 3 | 1 | 5 | 2 | 0 | 2 | 2 | 0 | 9 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 1 | 22 | 9 | 4 | 35 |
| 22 | 12 | 3 | 2 | 0 | 2 | 10 | 5 | 3 | 1 | 7 | 1 | 4 | 2 | 1 | 1 | 1 | 0 | 4 | 27 | 10 | 22 | 59 |
| X | 3 | 2 | 0 | 3 | 6 | 3 | 1 | 0 | 0 | 29 | 9 | 38 | 0 | 0 | 0 | 2 | 1 | 1 | 38 | 18 | 42 | 98 |
| Y | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| all chrs. | 8 | 44 | 12 | 1 | 77 | 1 | 0 | 0 | 0 | 3 | 7 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 12 | 128 | 13 | 153 |
| summary | 2917 | 1364 | 95 | 373 | 219 | 127 | 89 | 39 | 1 | 258 | 57 | 149 | 66 | 15 | 7 | 75 | 286 | 119 | 3778 | 1980 | 498 | 6256 |
