Familial syndromic esophageal atresia maps to 2p23-p24

  • Jacopo Celli*
  • , Ellen Van Beusekom
  • , Raoul C.M. Hennekam
  • , M. Esther Gallardo
  • , Dominique F.C.M. Smeets
  • , Santiago Rodríguez De Córdoba
  • , Jeffrey W. Innis
  • , Moshe Frydman
  • , Rainer König
  • , Helen Kingston
  • , John Tolmie
  • , Lutgarde C.P. Govaerts
  • , Hans Van Bokhoven
  • , Han G. Brunner
  • *Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Esophageal atresia (EA) is a common life-threatening congenital anomaly that occurs in 1/3,000 newborns. Little is known of the genetic factors that underlie EA. Oculodigitoesophageoduodenal (ODED) syndrome (also known as 'Feingold syndrome') is a rare autosomal dominant disorder with digital abnormalities, microcephaly, short palpebral fissures, mild learning disability, and esophageal/duodenal atresia. We studied four pedigrees, including a three-generation Dutch family with 11 affected members. Linkage analysis was initially aimed at chromosomal regions harboring candidate genes for this disorder. Twelve different genomic regions covering 15 candidate genes (~15% of the genome) were excluded from involvement in the ODED syndrome. A subsequent nondirective mapping approach revealed evidence for linkage between the syndrome and marker D2S390 (maximum LOD score 4.51 at recombination fraction 0). A submicroscopic deletion in a fourth family with ODED provided independent confirmation of this genetic localization and narrowed the critical region to 7.3 cM in the 2p23-p24 region. These results show that haploinsufficiency for a gene or genes in 2p23-p24 is associated with syndromic EA.

Original languageEnglish
Pages (from-to)436-444
Number of pages9
JournalAmerican Journal of Human Genetics
Volume66
Issue number2
DOIs
StatePublished - 2000

Funding

FundersFunder number
Dutch Foundation for Scientific Research
Dutch Liver-Gut FoundationWS 97-81
Nederlandse Organisatie voor Wetenschappelijk Onderzoek901-04-183

    Fingerprint

    Dive into the research topics of 'Familial syndromic esophageal atresia maps to 2p23-p24'. Together they form a unique fingerprint.

    Cite this