Epigenetic efects of the mutations in patients with the RAS/MAPK syndromes

RAS/MAPK 综合征患者突变的表观遗传效应

• 批准号: 23791148
• 负责人: NIIHORI Tetsuya
• 金额: $ 2.75万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23791148/
• 关键词: 遺伝・先天異常学; RAS/MAPK症候群; RAS/MAPK; Noonan症候群; Costello症候群; CFC症候群; 先天奇形症候群

We identified a total of nine missense mutations in RIT1 gene, encoding a member of the RAS subfamily, in 17 of 180 individuals (9%) with Noonan syndrome and related conditions without mutations in known genes. Clinical manifestations in the mutation-positive individuals are consistent with those of Noonan syndrome, which are characterized by distinctive facial appearance, short stature and congenital heart defects. Seventy percent of mutation-positive individuals had hypertrophic cardiomyopathy, a high frequency compared with the 20% incidence in individuals with Noonan syndrome overall.

我们在180例Noonan综合征和相关疾病患者中发现了编码RAS亚家族成员的RIT1基因总共9个错义突变，其中17人(9%)没有已知基因突变。突变阳性个体的临床表现与Noonan综合征一致，其特征是面部外观独特，身材矮小和先天性心脏缺陷。70%的突变阳性个体患有肥厚型心肌病，与努南综合征患者20%的总体发病率相比，这是一个很高的频率。

项目成果

TBX1 mutation identified by exome sequencing in a Japanese family with 22q11.2 deletion syndrome-like craniofacial features and hypocalcemia.

• DOI: 10.1371/journal.pone.0091598
• 发表时间: 2014
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Ogata T;Niihori T;Tanaka N;Kawai M;Nagashima T;Funayama R;Nakayama K;Nakashima S;Kato F;Fukami M;Aoki Y;Matsubara Y
• 通讯作者: Matsubara Y

Shimosegawa T . Sequential analysis of amino acid substitutions with hepatitis B virus in association with nucleoside/nucleotide analog treatment detected by deep sequencing

下濑川 T.

• DOI: 10.1111/hepr.12168
• 发表时间: 2014
• 期刊: Hepatol Res
• 影响因子: 4.2
• 作者: Ninomiya M;Kondo Y;Niihori T;Nagashima T;Kogure T;Kakazu E;Kimura O;Aoki Y;Matsubara Y
• 通讯作者: Matsubara Y

A girl with Cardio-facio-cutaneous syndrome complicated with status epilepticus and acute encephalopathy

心面皮肤综合征合并癫痫持续状态和急性脑病女孩

• DOI: 10.1016/j.braindev.2012.12.007
• 发表时间: 2014
• 期刊: Brain Dev
• 作者: Wakusawa K;Kobayashi S;Abe Y;Tanaka S;Endo W;Inui T;Iwaki M;Watanabe S;T ogashi N;Nara T;Niihori T;Aoki Y;Haginoya K
• 通讯作者: Haginoya K

Prevalence and clinical features of Costello syndrome and cardio-facio-cutaneous syndrome in Japan

日本科斯特洛综合征和心面皮肤综合征的患病率和临床特征

• 发表时间: 2010
• 作者: Abe Y;et al
• 通讯作者: et al

エクソームシークエンスによるNoonan症候群新規原因遺伝子RIT1の同定

通过外显子组测序鉴定努南综合征的新致病基因 RIT1

• 发表时间: 2013
• 作者: 新堀哲也;青木洋子;番匠俊博;岡本伸彦;水野誠司;黒澤健司;緒方勤;高田史男;長谷川奉延;舟山亮;長嶋剛史;中山啓子;井上晋一;渡邊裕介;小椋利彦;松原洋一
• 通讯作者: 松原洋一