Zebrafish gene knockdowns imply roles for human YWHAG in infantile spasms and cardiomegaly

Yuta Komoike; Katsunori Fujii; Akira Nishimura; Yoko Hiraki; Michiko Hayashidani; Keiko Shimojima; Tsutomu Nishizawa; Kouji Higashi; Kumi Yasukawa; Hirotomo Saitsu; Noriko Miyake; Takeshi Mizuguchi; Naomichi Matsumoto; Makiko Osawa; Yoichi Kohno; Toru Higashinakagawa; Toshiyuki Yamamoto

doi:10.1002/dvg.20607

Zebrafish gene knockdowns imply roles for human YWHAG in infantile spasms and cardiomegaly

Genesis. 2010 Apr;48(4):233-43. doi: 10.1002/dvg.20607.

Authors

Yuta Komoike¹, Katsunori Fujii, Akira Nishimura, Yoko Hiraki, Michiko Hayashidani, Keiko Shimojima, Tsutomu Nishizawa, Kouji Higashi, Kumi Yasukawa, Hirotomo Saitsu, Noriko Miyake, Takeshi Mizuguchi, Naomichi Matsumoto, Makiko Osawa, Yoichi Kohno, Toru Higashinakagawa, Toshiyuki Yamamoto

Affiliation

¹ International Research and Educational Institute for Integrated Medical Sciences (IREIIMS), Tokyo Women's Medical University, Shinjuku-ward, Tokyo, Japan.

PMID: 20146355
DOI: 10.1002/dvg.20607

Abstract

Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder presenting with an elfin-like face, supravalvular aortic stenosis, a specific cognitive-behavioral profile, and infantile hypercalcemia. We encountered two WBS patients presenting with infantile spasms, which is extremely rare in WBS. Array comparative genomic hybridization (aCGH) and fluorescent in situ hybridization (FISH) analyses revealed atypical 5.7-Mb and 4.1-Mb deletions at 7q11.23 in the two patients, including the WBS critical region and expanding into the proximal side and the telomeric side, respectively. On the proximal side, AUTS2 and CALN1 may contribute to the phenotype. On the telomeric side, there are two candidate genes HIP1 and YWHAG. Because detailed information of them was unavailable, we investigated their functions using gene knockdowns of zebrafish. When zebrafish ywhag1 was knocked down, reduced brain size and increased diameter of the heart tube were observed, indicating that the infantile spasms and cardiomegaly seen in the patient with the telomeric deletion may be derived from haploinsufficiency of YWHAG.

2010 Wiley-Liss, Inc.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

14-3-3 Proteins / genetics*
14-3-3 Proteins / metabolism
Animals
Brain / metabolism
Brain / pathology
Calmodulin / genetics
Calmodulin / metabolism
Cardiomegaly / genetics*
Cardiomegaly / metabolism
Cardiomegaly / pathology
Chromosome Deletion
Chromosomes, Human, Pair 7 / genetics
Chromosomes, Human, Pair 7 / metabolism
Comparative Genomic Hybridization
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism
Female
Gene Knockdown Techniques
Humans
Infant
Infant, Newborn
Male
Myocardium / metabolism
Myocardium / pathology
Oligonucleotide Array Sequence Analysis
Organ Size / genetics
Spasms, Infantile / genetics*
Spasms, Infantile / metabolism
Spasms, Infantile / pathology
Telomere / genetics
Telomere / metabolism
Telomere / pathology
Williams Syndrome / genetics*
Williams Syndrome / metabolism
Williams Syndrome / pathology
Zebrafish / genetics*
Zebrafish / metabolism
Zebrafish Proteins / genetics*
Zebrafish Proteins / metabolism

Substances

14-3-3 Proteins
CALN1 protein, human
Calmodulin
DNA-Binding Proteins
HIP1 protein, human
Zebrafish Proteins