Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Nov;88(5):405-15.
doi: 10.1111/cge.12596. Epub 2015 May 1.

A review of craniofacial disorders caused by spliceosomal defects

D Lehalle  1 , D Wieczorek  2 , R M Zechi-Ceide  3 , M R Passos-Bueno  4 , S Lyonnet  1   5   6 , J Amiel  1   5   6 , C T Gordon  5   6
Affiliations
Review

A review of craniofacial disorders caused by spliceosomal defects

D Lehalle et al. Clin Genet. 2015 Nov.

Abstract

The spliceosome is a large ribonucleoprotein complex that removes introns from pre-mRNA transcripts. Mutations in EFTUD2, encoding a component of the major spliceosome, have recently been identified as the cause of mandibulofacial dysostosis, Guion-Almeida type (MFDGA), characterized by mandibulofacial dysostosis, microcephaly, external ear malformations and intellectual disability. Mutations in several other genes involved in spliceosomal function or linked aspects of mRNA processing have also recently been identified in human disorders with specific craniofacial malformations: SF3B4 in Nager syndrome, an acrofacial dysostosis (AFD); SNRPB in cerebrocostomandibular syndrome, characterized by Robin sequence and rib defects; EIF4A3 in the AFD Richieri-Costa-Pereira syndrome, characterized by Robin sequence, median mandibular cleft and limb defects; and TXNL4A in Burn-McKeown syndrome, involving specific craniofacial dysmorphisms. Here, we review phenotypic and molecular aspects of these syndromes. Given the apparent sensitivity of craniofacial development to defects in mRNA processing, it is possible that mutations in other proteins involved in spliceosomal function will emerge in the future as causative for related human disorders.

Keywords: congenital malformations; craniofacial; mandibulofacial dysostosis; spliceosome.

PubMed Disclaimer

Similar articles

  • Spliceosomopathies and neurocristopathies: Two sides of the same coin?
    Beauchamp MC, Alam SS, Kumar S, Jerome-Majewska LA. Beauchamp MC, et al. Dev Dyn. 2020 Aug;249(8):924-945. doi: 10.1002/dvdy.183. Epub 2020 May 21. Dev Dyn. 2020. PMID: 32315467 Review.
  • Delineation of EFTUD2 haploinsufficiency-related phenotypes through a series of 36 patients.
    Lehalle D, Gordon CT, Oufadem M, Goudefroye G, Boutaud L, Alessandri JL, Baena N, Baujat G, Baumann C, Boute-Benejean O, Caumes R, Decaestecker C, Gaillard D, Goldenberg A, Gonzales M, Holder-Espinasse M, Jacquemont ML, Lacombe D, Manouvrier-Hanu S, Marlin S, Mathieu-Dramard M, Morin G, Pasquier L, Petit F, Rio M, Smigiel R, Thauvin-Robinet C, Vasiljevic A, Verloes A, Malan V, Munnich A, de Pontual L, Vekemans M, Lyonnet S, Attié-Bitach T, Amiel J. Lehalle D, et al. Hum Mutat. 2014 Apr;35(4):478-85. doi: 10.1002/humu.22517. Epub 2014 Mar 5. Hum Mutat. 2014. PMID: 24470203
  • Compound heterozygosity of low-frequency promoter deletions and rare loss-of-function mutations in TXNL4A causes Burn-McKeown syndrome.
    Wieczorek D, Newman WG, Wieland T, Berulava T, Kaffe M, Falkenstein D, Beetz C, Graf E, Schwarzmayr T, Douzgou S, Clayton-Smith J, Daly SB, Williams SG, Bhaskar SS, Urquhart JE, Anderson B, O'Sullivan J, Boute O, Gundlach J, Czeschik JC, van Essen AJ, Hazan F, Park S, Hing A, Kuechler A, Lohmann DR, Ludwig KU, Mangold E, Steenpaß L, Zeschnigk M, Lemke JR, Lourenco CM, Hehr U, Prott EC, Waldenberger M, Böhmer AC, Horsthemke B, O'Keefe RT, Meitinger T, Burn J, Lüdecke HJ, Strom TM. Wieczorek D, et al. Am J Hum Genet. 2014 Dec 4;95(6):698-707. doi: 10.1016/j.ajhg.2014.10.014. Epub 2014 Nov 26. Am J Hum Genet. 2014. PMID: 25434003 Free PMC article.
  • EIF4A3 deficient human iPSCs and mouse models demonstrate neural crest defects that underlie Richieri-Costa-Pereira syndrome.
    Miller EE, Kobayashi GS, Musso CM, Allen M, Ishiy FAA, de Caires LC Jr, Goulart E, Griesi-Oliveira K, Zechi-Ceide RM, Richieri-Costa A, Bertola DR, Passos-Bueno MR, Silver DL. Miller EE, et al. Hum Mol Genet. 2017 Jun 15;26(12):2177-2191. doi: 10.1093/hmg/ddx078. Hum Mol Genet. 2017. PMID: 28334780 Free PMC article.
  • Mandibulofacial Dysostosis with Microcephaly: Mutation and Database Update.
    Huang L, Vanstone MR, Hartley T, Osmond M, Barrowman N, Allanson J, Baker L, Dabir TA, Dipple KM, Dobyns WB, Estrella J, Faghfoury H, Favaro FP, Goel H, Gregersen PA, Gripp KW, Grix A, Guion-Almeida ML, Harr MH, Hudson C, Hunter AG, Johnson J, Joss SK, Kimball A, Kini U, Kline AD, Lauzon J, Lildballe DL, López-González V, Martinezmoles J, Meldrum C, Mirzaa GM, Morel CF, Morton JE, Pyle LC, Quintero-Rivera F, Richer J, Scheuerle AE, Schönewolf-Greulich B, Shears DJ, Silver J, Smith AC, Temple IK; UCLA Clinical Genomics Center; van de Kamp JM, van Dijk FS, Vandersteen AM, White SM, Zackai EH, Zou R; Care4Rare Canada Consortium; Bulman DE, Boycott KM, Lines MA. Huang L, et al. Hum Mutat. 2016 Feb;37(2):148-54. doi: 10.1002/humu.22924. Epub 2015 Nov 19. Hum Mutat. 2016. PMID: 26507355 Free PMC article. Review.
See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

Supplementary concepts

LinkOut - more resources