Hirschsprung Disease, Susceptibility To, 8

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Retrieved

2019-09-22

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Omim

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Genes

EDN3, EDNRB, GDNF, RET, ZEB2, NRG1, SOX10, SEMA3D, SEMA3C, ECE1, GFRA1, NKX2-1, CAVIN2, MIR206, GAL, FZD3, NTRK3, RELN, AFAP1-AS1, WNT3A, MIR369, NRSN1, CELSR3, ARID1B, GAP43, MIR218-1, BMI1, MIR195, MIR128-1, MED12, LCT-AS1, UTP25, IHH, L1CAM, ERBB2, ITGB1, CD14, AEBP2, PHOX2B, PAX3, NRTN, KIFBP, PROKR1, DSCAM, PIGV, ASCL1, BDNF, TCF4, PIGO, RASGEF1A, COMT, RMRP, CSGALNACT2, MITF, KITLG, KIAA0586, RAD51, RPGRIP1L, RIMBP2, PIGN, RAD51C, SETBP1, SH2B1, EXOC6B, TBX1, B9D1, PGAP2, UBE2T, RREB1, SNAI2, KIAA0556, KIR2DS4, KIR2DL1, KIR2DS1, MBTPS2, NPHP1, SEC24C, SF3B4, MAD2L2, PIBF1, PIGL, POLR2F, NAA10, MKKS, XRCC2, GJB6, UFD1, ZNF423, HIRA, KRAS, KIT, KIR3DL1, CEP104, TMEM216, VRK2, TMEM138, CSPP1, AHI1, ARMC9, DDX59, BRIP1, DHCR7, SLX4, ABHD1, CREBBP, PIGY, TMEM67, PGAP3, CEP41, B3GALT6, CEP120, ARX, APLF, ARL13B, CALB2, HYLS1, BRCA2, BRCA1, JMJD1C, MYO1H, ATRX, PIGW, ARVCF, ARL3, LINC00327, ACTG2, TCTN2, CEP290, FANCE, GATA1, FANCF, FANCG, CC2D2A, FOXF1, SALL4, INPP5E, GJB2, PALB2, FANCI, GP1BB, RFWD3, FANCL, MKS1, BCOR, FANCB, SLC6A8, FANCD2, FANCC, TCTN1, TMEM231, CPLANE1, EP300, TMEM237, ERCC4, FANCM, FANCA, ACHE, NTRK1, SLC9A3R2, NRG3, SCAF11, GEMIN2, GFRA4, SLC2A1, SEMA3A, MCS+9.7, BMP4, DNMT3B, FN1, HOXB5, S100A1, NID1, PTCH1, MIR215, PSPN, AKT1, NLGN1, IL11, PROK1, CALCA, MIR141, ICAM1, KCNN3, ANGPTL2, ELP1, PGP, PLAGL2, ARTN, RGS6, BMP2, S100B, MECP2, BMP10, MEG3, GLI1, CX3CL1, VAMP5, MIR483, NTF3, MIR770, ACTR2, AICDA, LRSAM1, SNRNP70, CHRNE, ITIH5, DNMT1, CYP2B6, COL6A1, COL6A2, DECR1, CTH, DCX, DVL2, ITPKC, ESR1, GFRA2, IARS2, GABRG2, ACKR3, FHL1, FGF1, NLGN2, FABP7, ERCC1, DNTT, ENO2, NOX5, EDNRA, DYRK1A, DVL3, DVL1, SVEP1, DUSP6, KCNG4, ZNF827, CDX2, MIR192, MIR214, ADRA2B, MIR24-1, MIR30A, MIR31, ADRA1A, MIR31HG, MIR431, MIR488, COL6A4P2, MIR637, MIR939, C17orf107, MIR1324, HOTTIP, MTRNR2L12, ADARB1, ACTB, FALEC, LINC01844, CBSL, ALK, MIR150, CDX1, MIR146A, TSGA13, CD34, CCK, PROKR2, CBS, GPR42, CAV1, CASR, KCNG3, NLRP6, CAPN1, BRS3, DOK6, BMP5, FGD2, BBS2, ASS1, CCDC66, COL6A4P1, RBPMS2, APP, GLI3, FOXA1, GRB10, WNT8A, CXCR4, MAPK10, DPF3, MAPK3, DVL1P1, PRKCI, FXYD1, CUL3, PLEK, IL1RL2, BANF1, HSPB3, PLAG1, LPAR2, DCLK1, KLF4, PIK3CG, SLIT2, HAND2, ROCK2, PIGA, TUBA1A, WNT1, ANO1, VIP, SCN1B, SCN10A, SIM2, RYR3, RYR2, RYR1, SOX2, SOX4, SOX9, ROCK1, SRY, SSTR4, STC1, SYP, ROBO1, RBP4, TCOF1, RBP3, TTF1, PTPRR, PTGER2, PTGES, PCDH9, PAX6, PCDHA9, IL17RA, BACE2, IL17A, AUTS2, IGF2, IGF1, SIGLEC8, CNTN6, HSPB2, HSPB1, TLX3, KCNK4, HOXA13, MNX1, SUFU, CNTN5, NLGN3, SLC6A20, GSTT1, GSTP1, GSTM1, ITGB2, JAG2, UBR4, CXCR6, EIF4A3, NUP98, ARNT2, NOTCH1, AKT3, NOS2, NOS1, NGF, MT1A, TRAF3IP2, KCNH2, MCC, MAP2, PRDX3, STMN2, INMT, ZNF609, SMAD1, PLCB1, KCNJ12, ABO

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Description

The disorder described by Hirschsprung (1888) and known as Hirschsprung disease or aganglionic megacolon is characterized by congenital absence of intrinsic ganglion cells in the myenteric (Auerbach) and submucosal (Meissner) plexuses of the gastrointestinal tract. Patients are diagnosed with the short-segment form (S-HSCR, approximately 80% of cases) when the aganglionic segment does not extend beyond the upper sigmoid, and with the long-segment form (L-HSCR) when aganglionosis extends proximal to the sigmoid. Total colonic aganglionosis and total intestinal HSCR also occur (Amiel et al., 2008).

Isolated HSCR appears to be of complex nonmendelian inheritance with low sex-dependent penetrance and variable expression according to the length of the aganglionic segment, suggestive of the involvement of one or more genes with low penetrance (Amiel et al., 2008).

For a general description and a discussion of genetic heterogeneity of Hirschsprung disease (HSCR), see 142623.

Mapping

Carrasquillo et al. (2002) conducted a genomewide association study in 43 Mennonite family trios using 2,083 microsatellites and single-nucleotide polymorphisms (SNPs) and a multipoint linkage disequilibrium method that searches for association arising from common ancestry. In addition to confirming susceptibility loci at 10q11, representing RET (164761), and 13q22, representing EDNRB (131244), they identified a susceptibility locus on 16q23 (lod = 3.01, P = 0.001) in which no gene known to confirm susceptibility to HSCR had been mapped. The authors suggested CDH13 (601364), a putative negative regulator of neural cell growth, and PLCG2 (600220), which functions in signal pathways that regulate neuronal differentiation, as candidate genes among 10 known genes found in the region of linkage.