Zebrafish gene knockdowns imply roles for human YWHAG in infantile spasms and cardiomegaly.
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.
International Research and Educational Institute for Integrated Medical Sciences (IREIIMS), Tokyo Women's Medical University, Shinjuku-ward, Tokyo, Japan.
Yuta
Y
Komoike
Katsunori
K
Fujii
Akira
A
Nishimura
Yoko
Y
Hiraki
Michiko
M
Hayashidani
Keiko
K
Shimojima
Tsutomu
T
Nishizawa
Kouji
K
Higashi
Kumi
K
Yasukawa
Hirotomo
H
Saitsu
Noriko
N
Miyake
Takeshi
T
Mizuguchi
Naomichi
N
Matsumoto
Makiko
M
Osawa
Yoichi
Y
Kohno
Toru
T
Higashinakagawa
Toshiyuki
T
Yamamoto
D048948:14-3-3 Proteins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002147:Calmodulin / Q000235:genetics / Q000378:metabolism; D006332:Cardiomegaly / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics / Q000378:metabolism; D055028:Comparative Genomic Hybridization; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size / Q000235:genetics; D013036:Spasms, Infantile / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016615:Telomere / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018980:Williams Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
D048948:14-3-3 Proteins; C428830:CALN1 protein, human; D002147:Calmodulin; D004268:DNA-Binding Proteins; C073368:HIP1 protein, human; D029961:Zebrafish Proteins