Clinical relevance of systematic phenotyping and exome sequencing in patients with short stature

Beitrag in einer Fachzeitschrift

Details zur Publikation

Autorinnen und Autoren: Hauer N, 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 C
Zeitschrift: Genetics in Medicine
Jahr der Veröffentlichung: 2018
Band: 20
Heftnummer: 6
Seitenbereich: 630-638
ISSN: 1098-3600


PurposeShort 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.MethodsWe 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.ResultsBy 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.ConclusionA 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.

FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Büttner, Christian
Lehrstuhl für Humangenetik
Dörr, Helmuth-Günther Prof. Dr.
Medizinische Fakultät
Ekici, Arif Bülent Dr. rer. nat.
Humangenetisches Institut
Ferrazzi, Fulvia Dr.
Humangenetisches Institut
Hauer, Nadine
Lehrstuhl für Humangenetik
Klinger, Patricia Dr. rer. nat.
Lehrstuhl für Funktionelle und Klinische Anatomie
Popp, Bernt Dr. med.
Humangenetisches Institut
Schuhmann, Sarah
Humangenetisches Institut
Sticht, Heinrich Prof. Dr.
Professur für Bioinformatik
Thiel, Christian PD Dr.
Medizinische Fakultät
Uebe, Steffen Dr. rer. nat.
Humangenetisches Institut

Einrichtungen weiterer Autorinnen und Autoren

Julius-Maximilians-Universität Würzburg
Otto-von-Guericke-Universität Magdeburg
Universidad Autónoma de Madrid (UAM)
Universität Duisburg-Essen (UDE)
Universität Leipzig
Universität Zürich (UZH)


Hauer, N., Popp, B., Schoeller, E., Schuhmann, S., Heath, K.E., Hisado-Oliva, A.,... Thiel, C. (2018). Clinical relevance of systematic phenotyping and exome sequencing in patients with short stature. Genetics in Medicine, 20(6), 630-638.

Hauer, Nadine, et al. "Clinical relevance of systematic phenotyping and exome sequencing in patients with short stature." Genetics in Medicine 20.6 (2018): 630-638.


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