Evolutionary conserved networks of human height identify multiple Mendelian causes of short stature

Journal article

Publication Details

Author(s): Hauer N, Popp B, Taher L, Vogl C, Dhandapany PS, Büttner C, Uebe S, Sticht H, Ferrazzi F, Ekici AB, De Luca A, Klinger P, Kraus C, Zweier C, Wiesener A, Jamra RA, Kunstmann E, Rauch A, Wieczorek D, Jung AM, Rohrer TR, Zenker M, Dörr HG, Reis A, Thiel C
Journal: European journal of human genetics
Publication year: 2019
ISSN: 1018-4813


Height is a heritable and highly heterogeneous trait. Short stature affects 3% of the population and in most cases is genetic in origin. After excluding known causes, 67% of affected individuals remain without diagnosis. To identify novel candidate genes for short stature, we performed exome sequencing in 254 unrelated families with short stature of unknown cause and identified variants in 63 candidate genes in 92 (36%) independent families. Based on systematic characterization of variants and functional analysis including expression in chondrocytes, we classified 13 genes as strong candidates. Whereas variants in at least two families were detected for all 13 candidates, two genes had variants in 6 (UBR4) and 8 (LAMA5) families, respectively. To facilitate their characterization, we established a clustered network of 1025 known growth and short stature genes, which yielded 29 significantly enriched clusters, including skeletal system development, appendage development, metabolic processes, and ciliopathy. Eleven of the candidate genes mapped to 21 of these clusters, including CPZ, EDEM3, FBRS, IFT81, KCND1, PLXNA3, RASA3, SLC7A8, UBR4, USP45, and ZFHX3. Fifty additional growth-related candidates we identified await confirmation in other affected families. Our study identifies Mendelian forms of growth retardation as an important component of idiopathic short stature.

FAU Authors / FAU Editors

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 Anatomie II
Popp, Bernt Dr. med.
Humangenetisches Institut
Sticht, Heinrich Prof. Dr.
Professur für Bioinformatik
Taher, Leila Prof. Dr.
Juniorprofessur für Bioinformatik
Thiel, Christian PD Dr.
Medizinische Fakultät
Uebe, Steffen Dr. rer. nat.
Humangenetisches Institut
Zweier, Christiane Prof. Dr.
Medizinische Fakultät

External institutions with authors

Casa Sollievo della Sofferenza
Institute for Stem Cell Science and Regenerative Medicine
Julius-Maximilians-Universität Würzburg
Otto-von-Guericke-Universität Magdeburg
Universität Duisburg-Essen
Universität Leipzig
Universitätsklinikum des Saarlandes
Universität Zürich (UZH)

How to cite

Hauer, N., Popp, B., Taher, L., Vogl, C., Dhandapany, P.S., Büttner, C.,... Thiel, C. (2019). Evolutionary conserved networks of human height identify multiple Mendelian causes of short stature. European journal of human genetics. https://dx.doi.org/10.1038/s41431-019-0362-0

Hauer, Nadine, et al. "Evolutionary conserved networks of human height identify multiple Mendelian causes of short stature." European journal of human genetics (2019).


Last updated on 2019-29-05 at 14:08