Tate Genshu, Tajiri Takuma, Kishimoto Koji, Mitsuya Toshiyuki
Department of Pathology, Showa University Fujigaoka Hospital, Fujigaoka 1-30, Aoba-Ku, Yokohama, 227-8501, Japan,
Med Mol Morphol. 2015 Jun;48(2):116-22. doi: 10.1007/s00795-014-0079-7. Epub 2014 Jun 10.
Asplenia syndrome (Ivemark syndrome) is a complex disorder composed of asplenia, malpositioning of the visceral organs and congenital heart defects. To elucidate the underlying molecular mechanism of asplenia syndrome, we herein analyzed the fatal case of a male neonate who exhibited three lobes of the left lung, asplenia and complex heart anomalies and died 6 hours after delivery. A whole-exome sequence (WES) analysis followed by Sanger sequence identified a heterozygous single nucleotide change (c.7829A>G) in exon 47 of the axonemal dynein heavy chain gene 5 (DNAH5), which results in the missense mutation of p.Glu2610Gly. This mutation was found only in the neonate, but not in his parents, implying de novo mutation of DNAH5 that codes dynein heavy chain, a component of outer dynein arm. The WES analysis also identified a heterozygous single nucleotide substitution (c.3697C>T) in the axonemal dynein heavy chain gene 7 (DNAH7), resulting in p.Arg1233Cys, and a rare SNP (c.2029G>A, p.Gly677Ser) of the axonemal dynein intermediate chain gene 1 (DNAI1) in the patient and his mother, but not in his father. The mutation of p.Glu2610Gly in DNAH5 is novel and we here present a first Japanese case of asplenia syndrome who exhibited a DNAH5 mutation.
无脾综合征（艾弗马克综合征）是一种复杂的疾病，由无脾、内脏器官异位和先天性心脏缺陷组成。为了阐明无脾综合征的潜在分子机制，我们在此分析了一名男性新生儿的致命病例，该新生儿左肺有三个叶、无脾且伴有复杂的心脏异常，出生后6小时死亡。全外显子组测序（WES）分析后进行桑格测序，在轴丝动力蛋白重链基因5（DNAH5）的第47外显子中鉴定出一个杂合单核苷酸变化（c.7829A>G），这导致了p.Glu2610Gly的错义突变。该突变仅在新生儿中发现，而在其父母中未发现，这意味着编码动力蛋白重链（外动力臂的一个组成部分）的DNAH5发生了新发突变。WES分析还在轴丝动力蛋白重链基因7（DNAH7）中鉴定出一个杂合单核苷酸替代（c.3697C>T），导致p.Arg1233Cys，并且在患者及其母亲中发现了轴丝动力蛋白中间链基因1（DNAI1）的一个罕见单核苷酸多态性（c.2029G>A，p.Gly677Ser），而在其父亲中未发现。DNAH5中p.Glu2610Gly的突变是新发现的，我们在此报告首例表现出DNAH5突变的日本无脾综合征病例。
