Oto-facial syndrome and esophageal atresia, intellectual disability and zygomatic anomalies - expanding the phenotypes associated with EFTUD2 mutations. - Archive ouverte HAL Access content directly
Journal Articles Orphanet Journal of Rare Diseases Year : 2013

Oto-facial syndrome and esophageal atresia, intellectual disability and zygomatic anomalies - expanding the phenotypes associated with EFTUD2 mutations.

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Kornelia Neveling
  • Function : Author
  • PersonId : 944054
Bert Callewaert
  • Function : Author
  • PersonId : 937815
Florian von Deimling
  • Function : Author
  • PersonId : 944056
Andreas Hehr
  • Function : Author
  • PersonId : 944057
Marie Falkenberg Smeland
  • Function : Author
  • PersonId : 944058
Rainer König
  • Function : Author
  • PersonId : 944059
Carlo Marcelis
  • Function : Author
  • PersonId : 944060
Maria Puiu
  • Function : Author
  • PersonId : 944061
Willie Reardon
  • Function : Author
  • PersonId : 944062
Marloes Steehouwer
  • Function : Author
  • PersonId : 944064
Christopher Teller
  • Function : Author
  • PersonId : 944065
Marcel Martin
  • Function : Author
  • PersonId : 944066
Ute Hehr
  • Function : Author
  • PersonId : 887990
Han Brunner
  • Function : Author
  • PersonId : 944068

Abstract

BACKGROUND: Mutations in EFTUD2 were proven to cause a very distinct mandibulofacial dysostosis type Guion-Almeida (MFDGA, OMIM #610536). Recently, gross deletions and mutations in EFTUD2 were determined to cause syndromic esophageal atresia (EA), as well. We set forth to find further conditions caused by mutations in the EFTUD2 gene (OMIM *603892). METHODS AND RESULTS: We performed exome sequencing in two familial cases with clinical features overlapping with MFDGA and EA, but which were previously assumed to represent distinct entities, a syndrome with esophageal atresia, hypoplasia of zygomatic complex, microcephaly, cup-shaped ears, congenital heart defect, and intellectual disability in a mother and her two children [AJMG 143A(11):1135-1142, 2007] and a supposedly autosomal recessive oto-facial syndrome with midline malformations in two sisters [AJMG 132(4):398-401, 2005]. While the analysis of our exome data was in progress, a recent publication made EFTUD2 mutations highly likely in these families. This hypothesis could be confirmed with exome as well as with Sanger sequencing. Also, in three further sporadic patients, clinically overlapping to these two families, de novo mutations within EFTUD2 were identified by Sanger sequencing. Our clinical and molecular workup of the patients discloses a broad phenotypic spectrum, and describes for the first time an instance of germline mosaicism for an EFTUD2 mutation. CONCLUSIONS: The clinical features of the eight patients described here further broaden the phenotypic spectrum caused by EFTUD2 mutations or deletions. We here show, that it not only includes mandibulofacial dysostosis type Guion-Almeida, which should be reclassified as an acrofacial dysostosis because of thumb anomalies (present in 12/35 or 34% of patients) and syndromic esophageal atresia [JMG 49(12). 737-746, 2012], but also the two new syndromes, namely oto-facial syndrome with midline malformations published by Mégarbané et al. [AJMG 132(4): 398-401, 2005] and the syndrome published by Wieczorek et al. [AJMG 143A(11): 1135-1142, 2007] The finding of mild phenotypic features in the mother of one family that could have been overlooked and the possibility of germline mosaicism in apparently healthy parents in the other family should be taken into account when counseling such families.
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Dates and versions

inserm-00849063 , version 1 (30-07-2013)

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Claudia Voigt, André Mégarbané, Kornelia Neveling, Johanna Christina Czeschik, Beate Albrecht, et al.. Oto-facial syndrome and esophageal atresia, intellectual disability and zygomatic anomalies - expanding the phenotypes associated with EFTUD2 mutations.. Orphanet Journal of Rare Diseases, 2013, 8 (1), pp.110. ⟨10.1186/1750-1172-8-110⟩. ⟨inserm-00849063⟩
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