KEGG   DISEASE: Heterotaxy
Entry
H00632                      Disease                                
Name
Heterotaxy;
Situs ambiguus
  Subgroup
Right atrial isomerism (RAI)
Description
Heterotaxy, or situs ambiguus, is an abnormal arrangement of the thoracic and abdominal viscera. The phenotype with mirror-image reversed left-right axis is called situs inversus, while partial alterations in the left-right organization is referred to as heterotaxy. Heterotaxy is associated with perturbation of nodal signaling during embryogenesis.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
 20 Developmental anomalies
  Structural developmental anomalies primarily affecting one body system
   Structural developmental anomalies of the circulatory system
    Structural developmental anomaly of heart or great vessels
     LA8Y  Other specified structural developmental anomaly of heart or great vessels
      H00632  Heterotaxy
Pathway-based classification of diseases [BR:br08402]
 Signal transduction
  nt06507  TGFB signaling
   H00632  Heterotaxy
Pathway
hsa04350  TGF-beta signaling pathway
Network
nt06507 TGFB signaling
Gene
(HTX1) ZIC3 [HSA:7547] [KO:K18487]
(HTX2) CFC1 [HSA:55997] [KO:K25454]
(HTX4) ACVR2B [HSA:93] [KO:K13596]
(HTX5) NODAL [HSA:4838] [KO:K04666]
(HTX6) CFAP53 [HSA:220136] [KO:K24225]
(HTX7) MMP21 [HSA:118856] [KO:K08000]
(HTX8) PKD1L1 [HSA:168507] [KO:K04987]
(HTX9) MNS1 [HSA:55329] [KO:K25441]
(HTX10) CFAP52 [HSA:146845] [KO:K24728]
(HTX11) CFAP45 [HSA:25790] [KO:K25551]
(HTX12) CIROP [HSA:100128908]
(RAI) GDF1 [HSA:2657] [KO:K05495]
Other DBs
ICD-11: LA8Y
ICD-10: Q89.3
MeSH: D059446
OMIM: 306955 605376 613751 270100 614779 616749 617205 618948 619607 619608 619702 208530
Reference
  Authors
Sutherland MJ, Ware SM
  Title
Disorders of left-right asymmetry: heterotaxy and situs inversus.
  Journal
Am J Med Genet C Semin Med Genet 151C:307-17 (2009)
DOI:10.1002/ajmg.c.30228
Reference
  Authors
Casey B
  Title
Genetics of human situs abnormalities.
  Journal
Am J Med Genet 101:356-8 (2001)
DOI:10.1002/ajmg.1220
Reference
PMID:9354794 (HTX1)
  Authors
Gebbia M, Ferrero GB, Pilia G, Bassi MT, Aylsworth A, Penman-Splitt M, Bird LM, Bamforth JS, Burn J, Schlessinger D, Nelson DL, Casey B
  Title
X-linked situs abnormalities result from mutations in ZIC3.
  Journal
Nat Genet 17:305-8 (1997)
DOI:10.1038/ng1197-305
Reference
PMID:11062482 (HTX2)
  Authors
Bamford RN, Roessler E, Burdine RD, Saplakoglu U, dela Cruz J, Splitt M, Goodship JA, Towbin J, Bowers P, Ferrero GB, Marino B, Schier AF, Shen MM, Muenke M, Casey B
  Title
Loss-of-function mutations in the EGF-CFC gene CFC1 are associated with human left-right laterality defects.
  Journal
Nat Genet 26:365-9 (2000)
DOI:10.1038/81695
Reference
PMID:9916847 (HTX4)
  Authors
Kosaki R, Gebbia M, Kosaki K, Lewin M, Bowers P, Towbin JA, Casey B
  Title
Left-right axis malformations associated with mutations in ACVR2B, the gene for human activin receptor type IIB.
  Journal
Reference
PMID:19064609 (HTX5)
  Authors
Mohapatra B, Casey B, Li H, Ho-Dawson T, Smith L, Fernbach SD, Molinari L, Niesh SR, Jefferies JL, Craigen WJ, Towbin JA, Belmont JW, Ware SM
  Title
Identification and functional characterization of NODAL rare variants in heterotaxy and isolated cardiovascular malformations.
  Journal
Hum Mol Genet 18:861-71 (2009)
DOI:10.1093/hmg/ddn411
Reference
PMID:22577226 (HTX6)
  Authors
Perles Z, Cinnamon Y, Ta-Shma A, Shaag A, Einbinder T, Rein AJ, Elpeleg O
  Title
A human laterality disorder associated with recessive CCDC11 mutation.
  Journal
J Med Genet 49:386-90 (2012)
DOI:10.1136/jmedgenet-2011-100457
Reference
PMID:20413652 (RAI)
  Authors
Kaasinen E, Aittomaki K, Eronen M, Vahteristo P, Karhu A, Mecklin JP, Kajantie E, Aaltonen LA, Lehtonen R
  Title
Recessively inherited right atrial isomerism caused by mutations in growth/differentiation factor 1 (GDF1).
  Journal
Hum Mol Genet 19:2747-53 (2010)
DOI:10.1093/hmg/ddq164
Reference
PMID:26429889 (HTX7)
  Authors
Perles Z, Moon S, Ta-Shma A, Yaacov B, Francescatto L, Edvardson S, Rein AJ, Elpeleg O, Katsanis N
  Title
A human laterality disorder caused by a homozygous deleterious mutation in MMP21.
  Journal
J Med Genet 52:840-7 (2015)
DOI:10.1136/jmedgenet-2015-103336
Reference
PMID:27616478 (HTX8)
  Authors
Vetrini F, D'Alessandro LC, Akdemir ZC, Braxton A, Azamian MS, Eldomery MK, Miller K, Kois C, Sack V, Shur N, Rijhsinghani A, Chandarana J, Ding Y, Holtzman J, Jhangiani SN, Muzny DM, Gibbs RA, Eng CM, Hanchard NA, Harel T, Rosenfeld JA, Belmont JW, Lupski JR, Yang Y
  Title
Bi-allelic Mutations in PKD1L1 Are Associated with Laterality Defects in Humans.
  Journal
Am J Hum Genet 99:886-893 (2016)
DOI:10.1016/j.ajhg.2016.07.011
Reference
PMID:31534215 (HTX9)
  Authors
Leslie JS, Rawlins LE, Chioza BA, Olubodun OR, Salter CG, Fasham J, Jones HF, Cross HE, Lam S, Harlalka GV, Muggenthaler MMA, Crosby AH, Baple EL
  Title
MNS1 variant associated with situs inversus and male infertility.
  Journal
Eur J Hum Genet 28:50-55 (2020)
DOI:10.1038/s41431-019-0489-z
Reference
PMID:33139725 (HTX11)
  Authors
Dougherty GW, Mizuno K, Nothe-Menchen T, Ikawa Y, Boldt K, Ta-Shma A, Aprea I, Minegishi K, Pang YP, Pennekamp P, Loges NT, Raidt J, Hjeij R, Wallmeier J, Mussaffi H, Perles Z, Elpeleg O, Rabert F, Shiratori H, Letteboer SJ, Horn N, Young S, Strunker T, Stumme F, Werner C, Olbrich H, Takaoka K, Ide T, Twan WK, Biebach L, Grosse-Onnebrink J, Klinkenbusch JA, Praveen K, Bracht DC, Hoben IM, Junger K, Gutzlaff J, Cindric S, Aviram M, Kaiser T, Memari Y, Dzeja PP, Dworniczak B, Ueffing M, Roepman R, Bartscherer K, Katsanis N, Davis EE, Amirav I, Hamada H, Omran H
  Title
CFAP45 deficiency causes situs abnormalities and asthenospermia by disrupting an axonemal adenine nucleotide homeostasis module.
  Journal
Nat Commun 11:5520 (2020)
DOI:10.1038/s41467-020-19113-0
Reference
PMID:34903892 (HTX12)
  Authors
Szenker-Ravi E, Ott T, Khatoo M, de Bellaing AM, Goh WX, Chong YL, Beckers A, Kannesan D, Louvel G, Anujan P, Ravi V, Bonnard C, Moutton S, Schoen P, Fradin M, Colin E, Megarbane A, Daou L, Chehab G, Di Filippo S, Rooryck C, Deleuze JF, Boland A, Arribard N, Eker R, Tohari S, Ng AY, Rio M, Lim CT, Eisenhaber B, Eisenhaber F, Venkatesh B, Amiel J, Crollius HR, Gordon CT, Gossler A, Roy S, Attie-Bitach T, Blum M, Bouvagnet P, Reversade B
  Title
Discovery of a genetic module essential for assigning left-right asymmetry in humans and ancestral vertebrates.
  Journal
Nat Genet 54:62-72 (2022)
DOI:10.1038/s41588-021-00970-4
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