Orofacial Cleft 10

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

IRF6, MSX1, TP63, NECTIN1, CDH1, BMP4, DLX4, ARHGAP29, DLG1, CALML3, COTL1, TERT, TGFA, CLPTM1L, CSRP3, MTHFR, PHF8, RPE65, CKAP4, UVRAG, TGFB3, SUMO1, PART1, CHD7, PTCH1, TIMP2, FGFR1, MTR, MAFB, MMP3, NAT2, WNT9B, NAT1, TBX22, BHMT, CBS, HFM, BMP2, SYNJ2, IFT88, KISS1R, WNT3A, KLF17, PGAP2, ARTN, WNT5A, WNT3, B3GLCT, PRSS35, MIR494, TPM1, CPO, KLF4, RAB34, TINAGL1, ACSS2, GTPBP4, RIC1, SHTN1, GRHL3, VAX1, CAMKMT, SNAP91, POMT1, ADAMTS20, SAE1, WNT10A, DNAJC5, NECTIN4, BHMT2, RARA, TGFB1, SPP1, FGF10, FGF9, FGF8, FGF3, FGF2, STOM, DMD, DLX1, DEFB1, DCN, CLPTM1, CDH2, KRIT1, CALM3, CALM2, CALM1, BCL3, ARSD, AGRP, AFP, ABCA4, FGFR2, FOXE1, FLG, NME1, SPINK1, SPARC, SLC19A1, RYK, RAD51C, PCNA, PAX7, PAX3, NME2, NHLH1, FN1, MYH9, MTRR, MTHFD1, MMP13, MMP1, MID1, HTC2, GNRHR, GABRB3, CBSL

Drugs

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A number sign (#) is used with this entry because of evidence that orofacial cleft-10 (OFC10) is caused by mutation in the SUMO1 gene (601912) on chromosome 2q33. One such patient has been reported.

For a phenotypic description and a discussion of genetic heterogeneity of nonsyndromic cleft lip/palate (CL/P), see 119530.

Clinical Features

Alkuraya et al. (2006) identified a 5-year-old Caucasian girl with a unilateral cleft lip and palate (primary and secondary) who was otherwise phenotypically normal. Her karyotype was 46,XX,t(2;8)(q33.1;q24.3), and array CGH analysis was normal.

Molecular Genetics

Alkuraya et al. (2006) showed that the balanced translocation in a girl with orofacial cleft disrupted the SUMO1 gene, leading to haploinsufficiency confirmed by RNA and protein studies (601912.0001).

Animal Model

Alkuraya et al. (2006) found Sumo1 to be expressed on mouse embryonic day 13.5 in the upper lip, primary palate, and medial edge epithelia of the secondary palate. At embryonic day 14.5, expression of Sumo1 could be seen in the medial edge epithelial seam using section in situ hybridization. Generation of mice carrying the Sumo1 hypomorphic allele resulted in an incidence of 8.7%, or 4 of 46 pups, with cleft palate or oblique facial cleft, compared with none in more than 100 wildtype mice. In addition, the genotype distribution from heterozygous crosses at P1 (1:1.15:0.75) deviated from the expected 1:2:1. Both embryonic demise between embryonic days 13.5 and 18.5 and immediate postnatal demise were noted for Sumo1 hetero- and homozygotes, indicating that Sumo1 is required for developmental functions besides palatogenesis. Alkuraya et al. (2006) found that heterozygotes for both Sumo1 and Eya1 (601653) haploinsufficiency had a much higher incidence of cleft palate (36%) than either Sumo1-haploinsufficient heterozygotes (8.7%) or Eya1-deficient heterozygotes (0.0%). Additionally, Alkuraya et al. (2006) found that Eya1 is a substrate for sumoylation with Sumo1 in vivo.