Familial Syndromic Esophageal Atresia Maps to 2p23-p24

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 abnorm...

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Bibliographic Details
Published in:	American journal of human genetics 2000-02, Vol.66 (2), p.436-444
Main Authors:	Celli, Jacopo, van Beusekom, Ellen, Hennekam, Raoul C.M., Gallardo, M. Esther, Smeets, Dominique F.C.M., de Córdoba, Santiago Rodríguez, Innis, Jeffrey W., Frydman, Moshe, König, Rainer, Kingston, Helen, Tolmie, John, Govaerts, Lutgarde C.P., van Bokhoven, Hans, Brunner, Han G.
Format:	Article
Language:	eng
Subjects:	Abnormalities, Multiple - genetics Animals Base Sequence Biological and medical sciences Chromosome Mapping Chromosomes, Human, Pair 2 - genetics Cloning, Molecular Complex syndromes Esophageal atresia Esophageal Atresia - genetics Female Fluorescence in situ hybridization Genes, Dominant - genetics Homeodomain Proteins - genetics Humans In Situ Hybridization, Fluorescence Limb abnormalities Linkage Lod Score Male Medical genetics Medical sciences Mice Mice, Knockout Microcephaly Microdeletion Molecular Sequence Data Nerve Tissue Proteins - genetics Netherlands Pedigree Phenotype Sequence Deletion - genetics Syndrome
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Summary:	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.
ISSN:	0002-9297 1537-6605