title: A maternally inherited chromosome 18q22.1 deletion in a male with late-presenting diaphragmatic hernia and microphthalmia-evaluation of DSEL as a candidate gene for the diaphragmatic defect.
abstract: Using an Affymetrix GeneChip(R) Human Mapping 100K Set to study a patient with a late-presenting, right-sided diaphragmatic hernia and microphthalmia, we found a maternally inherited deletion that was 2.7 Mb in size at chromosome 18q22.1. Mapping of this deletion using fluorescence in situ hybridization revealed three deleted genes-CDH19, DSEL, and TXNDC10, and one gene that contained the deletion breakpoint, CCDC102B. We selected DSEL for further study in 125 patients with diaphragmatic hernias, as it is involved in the synthesis of decorin, a protein that is required for normal collagen formation and that is upregulated during myogenesis. We found p.Met14Ile in an unrelated patient with a late-presenting, anterior diaphragmatic hernia. In the murine diaphragm, Dsel was only weakly expressed at the time of diaphragm closure and its expression in C2C12 myoblast cells did not change significantly during myoblast differentiation, thus reducing the likelihood that the gene is involved in myogenesis of the diaphragm. Although it is possible that the 18q22.1 deletion and haploinsufficiency for DSEL contributed to the diaphragmatic defect in the patient, a definite role for DSEL and decorin in the formation of the collagen-containing, central tendon of the diaphragm has not yet been established.
authors.affiliation: Department of Pediatrics, Division of Genetics, University of California, San Francisco, California 94143-0748, USA.
authors.forename: Hatem
authors.initials: H
authors.lastname: Zayed
authors.forename: Ryan
authors.initials: R
authors.lastname: Chao
authors.forename: Ali
authors.initials: A
authors.lastname: Moshrefi
authors.forename: Nelson
authors.initials: N
authors.lastname: Lopezjimenez
authors.forename: Allen
authors.initials: A
authors.lastname: Delaney
authors.forename: Justin
authors.initials: J
authors.lastname: Chen
authors.forename: Gary M
authors.initials: GM
authors.lastname: Shaw
authors.forename: Anne M
authors.initials: AM
authors.lastname: Slavotinek
mesh_terms: D017668:Age of Onset; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D020029:Base Pairing / Q000235:genetics; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D002872:Chromosome Deletion; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D003964:Diaphragm / Q000002:abnormalities / Q000196:embryology / Q000473:pathology; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D006548:Hernia, Diaphragmatic / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D040582:Inheritance Patterns / Q000235:genetics*; D008297:Male; D051379:Mice; D008850:Microphthalmos / Q000150:complications* / Q000235:genetics; D008969:Molecular Sequence Data; D009035:Mothers; D009693:Nucleic Acid Hybridization; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004268:DNA-Binding Proteins