A new case of Smith‐Kingsmore syndrome with somatic MTOR pathogenic variant expands the phenotypic spectrum to lateralized overgrowth
A new case of Smith‐Kingsmore syndrome with somatic MTOR pathogenic variant expands the phenotypic spectrum to lateralized overgrowth
复制标题
带有体细胞 MTOR 致病性变异的 Smith-Kingsmore 综合征新病例将表型谱扩展到偏侧过度生长
DOI：
10.1111/cge.13931
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发表时间：
2021
影响因子：
3.5
通讯作者：
A. Mussa
中科院分区：
文献类型：
--
作者：
D. Carli;G. Ferrero;Anna Fusillo;P. Coppo;Roberta La Selva;F. Zinali;S. Cardaropoli;C. Ranieri;M. Iacoviello;N. Resta;A. Mussa
史密斯-金斯莫尔综合征（SKS）是一种罕见的常染色体显性遗传病，由染色体1 p36上的哺乳动物雷帕霉素靶蛋白（MTOR）中的杂合子生殖系激活致病性变体引起。到目前为止，已经描述了一些播散性嵌合体患者，与生殖细胞病例相比，他们似乎表现出不同的表型。在这里，我们报告了第六例播散性镶嵌型MTOR致病性变异，一名7岁男孩，患有半侧巨脑畸形、癫痫、发育迟缓、伊藤黑素减少症和偏侧过度生长。基因检测揭示了MTOR中的致病性变体（c.4448G > A，p.Cys1483Tyr），其在从皮肤样品中提取的DNA中的频率为32%，在唾液中为3%，在血液中为0.46%。在我们的患者中观察到的临床特征进一步证实了生殖系和嵌合型SKS病例表型表现的差异。此外，偏侧过度生长，一个发现从未描述到目前为止，在SKS，进一步扩大了SKS的表型谱，并允许包括MTOR致病变异体之间的几个原因不对称的身体过度生长。
Smith‐Kingsmore syndrome (SKS) is a rare autosomal dominant disorder caused by heterozygous germline activating pathogenic variants in mammalian target of rapamycin (MTOR) on chromosome 1p36. A few patients with disseminated mosaicism have been described so far and they seem to display a different phenotype when compared to germline cases. Here we report the sixth case with a disseminated mosaic MTOR pathogenic variant, a 7‐year‐old boy with hemimegalencephaly, epilepsy, developmental delay, hypomelanosis of Ito, and lateralized overgrowth. Genetic testing revealed a pathogenic variant (c.4448G > A, p.Cys1483Tyr) in MTOR with a frequency of 32% in the DNA extracted from a skin sample, 3% in saliva and 0.46% in blood. The clinical features observed in our patient further corroborate the existence of differences in phenotypic presentation of germline and mosaic SKS cases. Moreover, lateralized overgrowth, a finding never described so far in SKS, further expands the phenotypic spectrum of SKS and allows the inclusion of MTOR pathogenic variants among the several causes of asymmetric body overgrowth.
影响因子：
29
作者：
Mirzaa GM;Campbell CD;Solovieff N;Goold C;Jansen LA;Menon S;Timms AE;Conti V;Biag JD;Adams C;Boyle EA;Collins S;Ishak G;Poliachik S;Girisha KM;Yeung KS;Chung BHY;Rahikkala E;Gunter SA;McDaniel SS;Macmurdo CF;Bernstein JA;Martin B;Leary R;Mahan S;Liu S;Weaver M;Doerschner M;Jhangiani S;Muzny DM;Boerwinkle E;Gibbs RA;Lupski JR;Shendure J;Saneto RP;Novotny EJ;Wilson CJ;Sellers WR;Morrissey M;Hevner RF;Ojemann JG;Guerrini R;Murphy LO;Winckler W;Dobyns WB
通讯作者：
Dobyns WB