Clinical relevance of systematic phenotyping and exome sequencing in patients with short stature.
Clinical relevance of systematic phenotyping and exome sequencing in patients with short stature.
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DOI：
10.1038/gim.2017.159
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发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Thiel CT
中科院分区：
文献类型：
--
作者：
Hauer NN;Popp B;Schoeller E;Schuhmann S;Heath KE;Hisado-Oliva A;Klinger P;Kraus C;Trautmann U;Zenker M;Zweier C;Wiesener A;Abou Jamra R;Kunstmann E;Wieczorek D;Uebe S;Ferrazzi F;Büttner C;Ekici AB;Rauch A;Sticht H;Dörr HG;Reis A;Thiel CT
身材矮小是患者及其家属高度关注的常见病症。大多数是遗传性的，但由于临床和遗传异质性，根本原因往往难以捉摸。我们系统地对 565 名身材矮小的常见非遗传原因排除的患者进行了表型分析，选择了 200 名有代表性的患者进行全外显子组测序，并分析了已识别的致病性变异以及受影响基因与生长的功能相关性。通过标准的针对性诊断和表型评估，我们在 565 名患者中仅确定了 13.6% 的已知病因。对 200 名患者进行全外显子组测序，发现其中 16.5% 的患者已知身材矮小基因存在其他突变，而这些患者仅表现出部分症状。在 200 名患者中，我们的研究结果对 15.5% 具有显着的临床相关性。隐性骨骼发育不良等位基因的杂合携带者占病例的 3.5%。系统表型分析、靶向基因检测和全外显子组测序相结合的方法可以识别至少 33% 病例中身材矮小的根本原因，使医生能够改进诊断、治疗和遗传咨询。外显子组测序显着提高了诊断率，从而提高了身材矮小患者的护理水平。
Short stature is a common condition of great concern to patients and their families. Mostly genetic in origin, the underlying cause often remains elusive due to clinical and genetic heterogeneity. We systematically phenotyped 565 patients where common nongenetic causes of short stature were excluded, selected 200 representative patients for whole-exome sequencing, and analyzed the identified variants for pathogenicity and the affected genes regarding their functional relevance for growth. By standard targeted diagnostic and phenotype assessment, we identified a known disease cause in only 13.6% of the 565 patients. Whole-exome sequencing in 200 patients identified additional mutations in known short-stature genes in 16.5% of these patients who manifested only part of the symptomatology. In 15.5% of the 200 patients our findings were of significant clinical relevance. Heterozygous carriers of recessive skeletal dysplasia alleles represented 3.5% of the cases. A combined approach of systematic phenotyping, targeted genetic testing, and whole-exome sequencing allows the identification of the underlying cause of short stature in at least 33% of cases, enabling physicians to improve diagnosis, treatment, and genetic counseling. Exome sequencing significantly increases the diagnostic yield and consequently care in patients with short stature.
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影响因子：
3.2
作者：
Guo MH;Shen Y;Walvoord EC;Miller TC;Moon JE;Hirschhorn JN;Dauber A
通讯作者：
Dauber A
影响因子：
51.1
作者：
Green, Jane;Cairns, Benjamin J.;Casabonne, Delphine;Wright, F. Lucy;Reeves, Gillian;Beral, Valerie
通讯作者：
Beral, Valerie
影响因子：
3.7
作者：
Moog U;Bierhals T;Brand K;Bautsch J;Biskup S;Brune T;Denecke J;de Die-Smulders CE;Evers C;Hempel M;Henneke M;Yntema H;Menten B;Pietz J;Pfundt R;Schmidtke J;Steinemann D;Stumpel CT;Van Maldergem L;Kutsche K
通讯作者：
Kutsche K
影响因子：
9.8
作者：
Lederer, Damien;Grisart, Bernard;Verellen-Dumoulin, Christine
通讯作者：
Verellen-Dumoulin, Christine
DOI：
10.1159/000316130
发表时间：
2010-01-01
期刊：
CURRENT INDICATIONS FOR GROWTH HORMONE THERAPY, SECOND EDITION
影响因子：
--
作者：
Richmond, Erick;Rogol, Alan D.
通讯作者：
Rogol, Alan D.