Novel missense mutation in DLL4 in a Japanese sporadic case of Adams-Oliver syndrome

Miwako Nagasaka, Mariko Ikeda, Hidehito Inagaki, Yuya Ouchi, Daisuke Kurokawa, Keiji Yamana, Risa Harada, Kandai Nozu, Yoshitada Sakai, Sushil K. Mishra, Yoshiki Yamaguchi, Ichiro Morioka, Tatsushi Toda, Hiroki Kurahashi, Kazumoto Iijima

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Adams-Oliver syndrome (AOS, OMIM; 100300) is a rare genetic disease characterized by aplasia cutis congenita, terminal transverse limb defects and cutis marmorata with vascular anomalies such as congenital heart defects. The etiology of this syndrome has remained largely unknown but defective Notch signaling during vascular formation has been suggested. Here we describe a sporadic Japanese newborn case with clinically diagnosed AOS. Trio whole-exome sequencing identified a de novo, novel, heterozygous missense mutation in the Delta-like 4 ligand gene (DLL4 c.572G>A, p.Arg191His) in the patient. DLL4 functions as a requisite ligand for NOTCH1 receptor, which is essential for vascular formation. Amino acid substitution of Arg191 to His was predicted by molecular models to interfere with direct binding between DLL4 and NOTCH1. DLL4 has recently been identified as a causative gene of an autosomal dominant type of AOS with milder symptoms. The case described here showed gradual recovery from skull defects after birth and no psychomotor developmental delay has been observed. This is the second report of an AOS case with DLL4 mutation, and the phenotypic characteristics between the two cases are compared and discussed.

Original languageEnglish
Pages (from-to)851-855
Number of pages5
JournalJournal of Human Genetics
Volume62
Issue number9
DOIs
Publication statusPublished - 01-09-2017

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Missense Mutation
Blood Vessels
Exome
Ectodermal Dysplasia
Genetic Databases
Dominant Genes
Inborn Genetic Diseases
Molecular Models
Congenital Heart Defects
Amino Acid Substitution
Rare Diseases
Skull
Extremities
Newborn Infant
Ligands
Mutation
Genes
Adams Oliver syndrome

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Nagasaka, Miwako ; Ikeda, Mariko ; Inagaki, Hidehito ; Ouchi, Yuya ; Kurokawa, Daisuke ; Yamana, Keiji ; Harada, Risa ; Nozu, Kandai ; Sakai, Yoshitada ; Mishra, Sushil K. ; Yamaguchi, Yoshiki ; Morioka, Ichiro ; Toda, Tatsushi ; Kurahashi, Hiroki ; Iijima, Kazumoto. / Novel missense mutation in DLL4 in a Japanese sporadic case of Adams-Oliver syndrome. In: Journal of Human Genetics. 2017 ; Vol. 62, No. 9. pp. 851-855.
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abstract = "Adams-Oliver syndrome (AOS, OMIM; 100300) is a rare genetic disease characterized by aplasia cutis congenita, terminal transverse limb defects and cutis marmorata with vascular anomalies such as congenital heart defects. The etiology of this syndrome has remained largely unknown but defective Notch signaling during vascular formation has been suggested. Here we describe a sporadic Japanese newborn case with clinically diagnosed AOS. Trio whole-exome sequencing identified a de novo, novel, heterozygous missense mutation in the Delta-like 4 ligand gene (DLL4 c.572G>A, p.Arg191His) in the patient. DLL4 functions as a requisite ligand for NOTCH1 receptor, which is essential for vascular formation. Amino acid substitution of Arg191 to His was predicted by molecular models to interfere with direct binding between DLL4 and NOTCH1. DLL4 has recently been identified as a causative gene of an autosomal dominant type of AOS with milder symptoms. The case described here showed gradual recovery from skull defects after birth and no psychomotor developmental delay has been observed. This is the second report of an AOS case with DLL4 mutation, and the phenotypic characteristics between the two cases are compared and discussed.",
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Nagasaka, M, Ikeda, M, Inagaki, H, Ouchi, Y, Kurokawa, D, Yamana, K, Harada, R, Nozu, K, Sakai, Y, Mishra, SK, Yamaguchi, Y, Morioka, I, Toda, T, Kurahashi, H & Iijima, K 2017, 'Novel missense mutation in DLL4 in a Japanese sporadic case of Adams-Oliver syndrome', Journal of Human Genetics, vol. 62, no. 9, pp. 851-855. https://doi.org/10.1038/jhg.2017.48

Novel missense mutation in DLL4 in a Japanese sporadic case of Adams-Oliver syndrome. / Nagasaka, Miwako; Ikeda, Mariko; Inagaki, Hidehito; Ouchi, Yuya; Kurokawa, Daisuke; Yamana, Keiji; Harada, Risa; Nozu, Kandai; Sakai, Yoshitada; Mishra, Sushil K.; Yamaguchi, Yoshiki; Morioka, Ichiro; Toda, Tatsushi; Kurahashi, Hiroki; Iijima, Kazumoto.

In: Journal of Human Genetics, Vol. 62, No. 9, 01.09.2017, p. 851-855.

Research output: Contribution to journalArticle

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T1 - Novel missense mutation in DLL4 in a Japanese sporadic case of Adams-Oliver syndrome

AU - Nagasaka, Miwako

AU - Ikeda, Mariko

AU - Inagaki, Hidehito

AU - Ouchi, Yuya

AU - Kurokawa, Daisuke

AU - Yamana, Keiji

AU - Harada, Risa

AU - Nozu, Kandai

AU - Sakai, Yoshitada

AU - Mishra, Sushil K.

AU - Yamaguchi, Yoshiki

AU - Morioka, Ichiro

AU - Toda, Tatsushi

AU - Kurahashi, Hiroki

AU - Iijima, Kazumoto

PY - 2017/9/1

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N2 - Adams-Oliver syndrome (AOS, OMIM; 100300) is a rare genetic disease characterized by aplasia cutis congenita, terminal transverse limb defects and cutis marmorata with vascular anomalies such as congenital heart defects. The etiology of this syndrome has remained largely unknown but defective Notch signaling during vascular formation has been suggested. Here we describe a sporadic Japanese newborn case with clinically diagnosed AOS. Trio whole-exome sequencing identified a de novo, novel, heterozygous missense mutation in the Delta-like 4 ligand gene (DLL4 c.572G>A, p.Arg191His) in the patient. DLL4 functions as a requisite ligand for NOTCH1 receptor, which is essential for vascular formation. Amino acid substitution of Arg191 to His was predicted by molecular models to interfere with direct binding between DLL4 and NOTCH1. DLL4 has recently been identified as a causative gene of an autosomal dominant type of AOS with milder symptoms. The case described here showed gradual recovery from skull defects after birth and no psychomotor developmental delay has been observed. This is the second report of an AOS case with DLL4 mutation, and the phenotypic characteristics between the two cases are compared and discussed.

AB - Adams-Oliver syndrome (AOS, OMIM; 100300) is a rare genetic disease characterized by aplasia cutis congenita, terminal transverse limb defects and cutis marmorata with vascular anomalies such as congenital heart defects. The etiology of this syndrome has remained largely unknown but defective Notch signaling during vascular formation has been suggested. Here we describe a sporadic Japanese newborn case with clinically diagnosed AOS. Trio whole-exome sequencing identified a de novo, novel, heterozygous missense mutation in the Delta-like 4 ligand gene (DLL4 c.572G>A, p.Arg191His) in the patient. DLL4 functions as a requisite ligand for NOTCH1 receptor, which is essential for vascular formation. Amino acid substitution of Arg191 to His was predicted by molecular models to interfere with direct binding between DLL4 and NOTCH1. DLL4 has recently been identified as a causative gene of an autosomal dominant type of AOS with milder symptoms. The case described here showed gradual recovery from skull defects after birth and no psychomotor developmental delay has been observed. This is the second report of an AOS case with DLL4 mutation, and the phenotypic characteristics between the two cases are compared and discussed.

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