Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome.
Expanding the genotypic and phenotypic spectrum in a diverse cohort of 104 individuals with Wiedemann-Steiner syndrome.
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DOI：
10.1002/ajmg.a.62124
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Quintero-Rivera F
中科院分区：
文献类型：
--
作者：
Sheppard SE;Campbell IM;Harr MH;Gold N;Li D;Bjornsson HT;Cohen JS;Fahrner JA;Fatemi A;Harris JR;Nowak C;Stevens CA;Grand K;Au M;Graham JM Jr;Sanchez-Lara PA;Campo MD;Jones MC;Abdul-Rahman O;Alkuraya FS;Bassetti JA;Bergstrom K;Bhoj E;Dugan S;Kaplan JD;Derar N;Gripp KW;Hauser N;Innes AM;Keena B;Kodra N;Miller R;Nelson B;Nowaczyk MJ;Rahbeeni Z;Ben-Shachar S;Shieh JT;Slavotinek A;Sobering AK;Abbott MA;Allain DC;Amlie-Wolf L;Au PYB;Bedoukian E;Beek G;Barry J;Berg J;Bernstein JA;Cytrynbaum C;Chung BH;Donoghue S;Dorrani N;Eaton A;Flores-Daboub JA;Dubbs H;Felix CA;Fong CT;Fung JLF;Gangaram B;Goldstein A;Greenberg R;Ha TK;Hersh J;Izumi K;Kallish S;Kravets E;Kwok PY;Jobling RK;Knight Johnson AE;Kushner J;Lee BH;Levin B;Lindstrom K;Manickam K;Mardach R;McCormick E;McLeod DR;Mentch FD;Minks K;Muraresku C;Nelson SF;Porazzi P;Pichurin PN;Powell-Hamilton NN;Powis Z;Ritter A;Rogers C;Rohena L;Ronspies C;Schroeder A;Stark Z;Starr L;Stoler J;Suwannarat P;Velinov M;Weksberg R;Wilnai Y;Zadeh N;Zand DJ;Falk MJ;Hakonarson H;Zackai EH;Quintero-Rivera F
Wiedemann-Steiner综合征（WSS）是由KMT 2A单等位基因变异引起的常染色体显性遗传疾病，其特征为智力残疾和高血压。我们对来自五大洲的104名WSS患者进行了一项回顾性、多中心、观察性研究，以描述不同人群中WSS的临床和分子谱，确定白色人与黑人土著有色人种个体相比可能更普遍的身体特征，描述基因型-表型相关性，定义发育里程碑，描述成年期的综合征，并检查临床医生的鉴别诊断。研究中观察到的82种变异中有69种（84%）以前未在文献中报告。队列中确定的常见临床特征包括：发育迟缓或智力残疾（97%）、便秘（63.8%）、发育不良（67.7%）、进食困难（66.3%）、肘关节肥大（57%）、身材矮小（57.8%）和椎体异常（46.9%）。行走和第一次说话的中位年龄分别为20个月和18个月。张力减退与功能丧失（LoF）变异相关，癫痫发作与非LoF变异相关。本研究在一个种族多样的队列中确定了基因型-表型相关性以及种族-面部特征相关性，并准确定义了WSS患者的发育轨迹、医学共病和长期结局。
Wiedemann-Steiner syndrome (WSS) is an autosomal dominant disorder caused by monoallelic variants in KMT2A and characterized by intellectual disability and hypertrichosis. We performed a retrospective, multicenter, observational study of 104 individuals with WSS from five continents to characterize the clinical and molecular spectrum of WSS in diverse populations, to identify physical features that may be more prevalent in White versus Black Indigenous People of Color individuals, to delineate genotype–phenotype correlations, to define developmental milestones, to describe the syndrome through adulthood, and to examine clinicians' differential diagnoses. Sixty-nine of the 82 variants (84%) observed in the study were not previously reported in the literature. Common clinical features identified in the cohort included: developmental delay or intellectual disability (97%), constipation (63.8%), failure to thrive (67.7%), feeding difficulties (66.3%), hypertrichosis cubiti (57%), short stature (57.8%), and vertebral anomalies (46.9%). The median ages at walking and first words were 20 months and 18 months, respectively. Hypotonia was associated with loss of function (LoF) variants, and seizures were associated with non-LoF variants. This study identifies genotype–phenotype correlations as well as race-facial feature associations in an ethnically diverse cohort, and accurately defines developmental trajectories, medical comorbidities, and long-term outcomes in individuals with WSS.
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影响因子：
3.7
作者：
Li N;Wang Y;Yang Y;Wang P;Huang H;Xiong S;Sun L;Cheng M;Song C;Cheng X;Ding Y;Chang G;Chen Y;Xu Y;Yu T;Yao RE;Shen Y;Wang X;Wang J
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30.8
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Andersson AK;Ma J;Wang J;Chen X;Gedman AL;Dang J;Nakitandwe J;Holmfeldt L;Parker M;Easton J;Huether R;Kriwacki R;Rusch M;Wu G;Li Y;Mulder H;Raimondi S;Pounds S;Kang G;Shi L;Becksfort J;Gupta P;Payne-Turner D;Vadodaria B;Boggs K;Yergeau D;Manne J;Song G;Edmonson M;Nagahawatte P;Wei L;Cheng C;Pei D;Sutton R;Venn NC;Chetcuti A;Rush A;Catchpoole D;Heldrup J;Fioretos T;Lu C;Ding L;Pui CH;Shurtleff S;Mullighan CG;Mardis ER;Wilson RK;Gruber TA;Zhang J;Downing JR;St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project
通讯作者：
St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project
DOI：
10.1038/s41436-020-0869-3
发表时间：
2020-10
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Kaseniit KE;Haque IS;Goldberg JD;Shulman LP;Muzzey D
通讯作者：
Muzzey D
DOI：
10.1126/science.aan4673
发表时间：
2019-11-01
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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通讯作者：
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影响因子：
9.8
作者：
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通讯作者：
Sadikovic, Bekim