22q13 deletion syndrome

From Infogalactic: the planetary knowledge core
Jump to: navigation, search
22q13 Deletion Syndrome
Classification and external resources
Specialty Lua error in Module:Wikidata at line 446: attempt to index field 'wikibase' (a nil value).
ICD-10 Q93
OMIM 606232
DiseasesDB 34793
Patient UK 22q13 deletion syndrome
MeSH C536801
GeneReviews
Orphanet 48652
[[[d:Lua error in Module:Wikidata at line 863: attempt to index field 'wikibase' (a nil value).|edit on Wikidata]]]

22q13 deletion syndrome (spoken as twenty-two q one three[1]) is a genetic disorder caused by deletions or rearrangements on the q terminal end (long arm) of chromosome 22. Any abnormal genetic variation in the q13 region that presents with significant manifestations (phenotype) typical of a terminal deletion should be diagnosed as 22q13 deletion syndrome. 22q13 deletion syndrome is often placed in the more general category of Phelan-McDermid Syndrome (abbreviated PMS), which includes some mutations and microdeletions. The PMS name is less precise, since there is disagreement among researchers as to which variants belong in the PMS category.[2] The Developmental Synaptopathies Consortium defines PMS as being caused by SHANK3 mutations, a definition that excludes terminal deletions. [3]

A prototypical terminal deletion of 22q13 can be uncovered by karyotype analysis, but many terminal and interstitial deletions are too small. The availability of DNA microarray technology for revealing multiple genetic problems simultaneously has been the diagnostic tool of choice. The falling cost for whole exome sequencing and, eventually, whole genome sequencing, may replace DNA microarray technology for candidate evaluation. However, fluorescence in situ hybridization (FISH) tests remain valuable for diagnosing cases of mosaicism (mosaic genetics) and chromosomal rearrangements (e.g., ring chromosome, unbalanced chromosomal translocation). Although early researchers sought a monogenic (single gene genetic disorder) explanation, recent studies have not supported that hypothesis (see Etiology, below).

22q13 deletion syndrome is characterized by global developmental delay, absent or severely delayed speech, and neonatal hypotonia.[4] There are approximately 1300 diagnosed cases of 22q13 deletion syndrome worldwide.

Characteristics

The core characteristics of 22q13 Deletion syndrome (listed above) have a major impact on the individual. However, in addition to these characteristics, there are other manifestations than may range from mild to severe:

Physical

Behavioral

  • Chewing on non food items: 85%
  • Delayed or unreliable toileting: 76%
  • Impulsive behaviors: 47%
  • Biting (self or others): 46%
  • Problems sleeping: 46%
  • Hair pulling: 41%
  • Autistic behaviors: 31%
  • Episodes of non-stop crying before age 5: 30%
  • Teeth grinding: (unknown) %

Etiology

Various deletions affect the terminal region of the long arm of chromosome 22 (the paternal chromosome in 75% of cases), from 22q13.3 to 22qter. Although the deletion is most typically a result of a de novo mutation, there is an inherited form resulting from familial chromosomal translocations involving the 22 chromosome. In the de novo form, the size of the terminal deletion is variable and can go from 130 Kb (130,000 base pairs) to 9 Mb. Deletions smaller than 1 Mb are very rare (about 3%). The remaining 97% of terminal deletions impact about 30 to 190 genes (see list, below). At one time it was thought that deletion size was not related to the core clinical features.[5] That observation lead to an emphasis on the SHANK3 gene, which resides close to the terminal end of chromosome 22. Interest in SHANK3 grew as it became associated with Autism Spectrum Disorder (ASD) and Schizophrenia.[6] SHANK3 mutations and microdeletions can produce a phenotype similar to 22q13 deletion syndrome (hence, its inclusion in the PMS category). However, recent work suggests that the phenotype associated with SHANK3 microdeletions and mutations may result from a molecular mechanism very different from that originally described for 22q13 deletion syndrome. The phenotype may result from an over-expression of isoforms (e.g., Shank3b and Shank3e) that interfere with spine development.[7] The traditional mechanism of 22q13 deletion syndrome is whole gene loss (haploinsufficiency). Finding cases of SHANK3 deletion without involvement of other genes highly and/or specifically expressed in the brain may be unrealistic because distal chromosome 22q is a gene rich region. Animal studies may be helpful, but genes on the rodent chromosomes are organized differently than human. Human induced pluripotent stem cell lines could be a more promising approach.

The core features of 22q13 deletion syndrome are somewhat dependent upon deletion size, and do not necessarily depend on the loss of SHANK3.[8][9][10] As noted above, the distal 1 Mb of 22q is a gene rich region. There are too few clinical cases to statistically measure the relationship between deletion size and phenotype in this region. A landmark study of induced pluripotent stem cell neurons cultured from patients with 22q13 deletion syndrome shows that restoration of the SHANK3 protein levels can rescue fewer than half the glutamate neurons of neocortex, another indication of the strong impact of other genes in the distal 1 Mb of chromosome 22.[11]

There is an interest in the impact of MAPK8IP2 (also called IB2) in 22q13 deletion syndrome.[12] MAPK8IP2 is especially interesting because it regulates the balance between NMDA receptors and AMPA receptors.[13] The genes SULT4A1[14] and PARVB[15] may cause 22q13 deletion syndrome in cases of more proximal interstitial and large terminal deletions.[10] There are about 187 protein coding genes in the 22q13 region.[16] A group of genes (MPPED1,[17] CYB5R3,[18] FBLN1,[19] NUP50,[20] C22orf9,[21] KIAA1644,[22] PARVB,[15] TRMU,[23] WNT7B[24] and ATXN10[25]), as well as microRNAs may all contribute to loss of language, a feature that does vary with deletion size.[26] The same study found that macrocephaly seen in 22q13 deletion syndrome patients may be associated with WNT7B.

Table of protein coding genes involved in 22q13 deletion syndrome (based on Human Genome Browser – hg38 assembly [27]). Underline identifies genes associated with autism. Bold identifies genes associated with hypotonia (based on Human Phenotype Browser [28] search for 'hypotonia' and the OMIM database [29]).

RABL2B ACR SHANK3 ARSA MAPK8IP2 CHKB CPT1B SYCE3 KLHDC7B ODF3B TYMP SCO2
NCAPH2 LMF2 MIOX ADM2 SBF1 PPP6R2 DENND6B PLXNB2 MAPK11 MAPK12 HDAC10 TUBGCP6
SELO TRABD PANX2 MOV10L1 MLC1 IL17REL PIM3 CRELD2 ALG12 ZBED4 BRD1 FAM19A5
FLJ32756 TBC1D22A CERK GRAMD4 CELSR1 TRMU BC069212 GTSE1 TTC38 PKDREJ CDPF1 PPARA
WNT7B ATXN10 FBLN1 RIBC2 SMC1B FAM118A UPK3A KIAA0930 NUP50 PHF21B PRR5-ARHGAP8 LDOC1L
KIAA1644 PARVG TRNA_SeC PARVB SAMM50 PNPLA3 PNPLA5 SULT4A1 EFCAB6 MPPED1 SCUBE1 TTLL12
TSPO MCAT BIK TTLL1 PACSIN2 ARFGAP3 A4GALT ATP5L2 DL490307 CYB5R3 RNU12 POLDIP3
SERHL2 RRP7A NFAM1 TCF20 CYP2D6 NDUFA6 SMDT1 FAM109B NAGA WBP2NL CENPM TNFRSF13C
SHISA8 SREBF2 CCDC134 MEI1 C22orf46 NHP2L1 XRCC6 DESI1 PMM1 CSDC2 POLR3H ACO2
PHF5A TOB2 TEF ZC3H7B RANGAP1 CHADL L3MBTL2 EP300 RBX1 DNAJB7 XPNPEP3 ST13
SLC25A17 MCHR1 MKL1 SGSM3 ADSL TNRC6B FAM83F GRAP2 ENTHD1 CACNA1I RPS19BP1 ATF4
SMCR7L MGAT3 TAB1 SNORD43 RPL3 PDGFB CBX7 APOBEC3H APOBEC3F APOBEC3D APOBEC3C APOBEC3B
CBX6 NPTXR DNAL4 SUN2 GTPBP1 JOSD1 TOMM22 CBY1 FAM227A DMC1 DDX17 KDELR3
KCNJ4 CSNK1E TMEM184B MAFF MAFF PLA2G6 BAIAP2L2 SLC16A8 PICK1 SOX10 POLR2F C22orf23
MICALL1 EIF3L ANKRD54 GALR3 GCAT H1F0 TRIOBP NOL12 LGALS1 SH3BP1 GGA1 LGALS2
CDC42EP1 CARD10 MFNG ELFN2 CYTH4

Incidence

The incidence of the 22q13 deletion syndrome is uncertain. The National Institutes of Health Office of Rare Diseases (http://rarediseases.info.nih.gov/) lists 22q13 deletion syndrome as a rare disease.

See also

Notes

  1. ↑ Technically, it should be spoken as twenty-two q one three
  2. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ https://www.rarediseasesnetwork.org/cms/dsc/About-Us (downloaded 21-September-2015)
  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  9. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  10. ↑ 10.0 10.1 Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ http://www.genecards.org/cgi-bin/carddisp.pl?gene=SULT4A1&search=a909593f05863155b816a8fb7654c03b
  15. ↑ 15.0 15.1 http://www.genecards.org/cgi-bin/carddisp.pl?gene=PARVB&search=6f331a34c3511163f07d03211274ad96
  16. ↑ http://genome.ucsc.edu/
  17. ↑ http://www.genecards.org/cgi-bin/carddisp.pl?gene=MPPED1&search=af0348b2e8f8bbe07815c7c4c35e1f8e
  18. ↑ http://www.genecards.org/cgi-bin/carddisp.pl?gene=CYB5R3&search=f30516afb414af5d738f38bfdee0a8b4
  19. ↑ http://www.genecards.org/cgi-bin/carddisp.pl?gene=FBLN1&search=31c50040405215fff62221f468762f78
  20. ↑ http://www.genecards.org/cgi-bin/carddisp.pl?gene=NUP50&search=ebf7ec6b4ee48d75243c7b448aa489a8
  21. ↑ http://www.genecards.org/cgi-bin/carddisp.pl?gene=KIAA0930&search=7fe64f97e1b1ff3046fce6978ce05ceb
  22. ↑ http://www.genecards.org/cgi-bin/carddisp.pl?gene=KIAA1644&search=7699c1245c9f84709a4902cb2643f900
  23. ↑ http://www.genecards.org/cgi-bin/carddisp.pl?gene=TRMU&search=dfaeaec9ab390a77b7713cddf9e0d842
  24. ↑ http://www.genecards.org/cgi-bin/carddisp.pl?gene=WNT7B&search=b9a837acec2f26b76076ecd2d3887361
  25. ↑ http://www.genecards.org/cgi-bin/carddisp.pl?gene=ATXN10&search=8085643553fd43eaabcf7fac1618ef13
  26. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  27. ↑ https://genome.ucsc.edu/index.html
  28. ↑ http://www.human-phenotype-ontology.org/
  29. ↑ http://www.omim.org/

References

  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • Lua error in package.lua at line 80: module 'strict' not found.
  • 22q13.org "22q13 deletion syndrome home"
  • Lua error in package.lua at line 80: module 'strict' not found.

External links

Retrieved from "https://infogalactic.com/w/index.php?title=22q13_deletion_syndrome&oldid=575026"