TY  - JOUR
A1  - Hauer, Nadine N.
A1  - Popp, Bernt
A1  - Schoeller, Eva
A1  - Schuhmann, Sarah
A1  - Heath, Karen E.
A1  - Hisado-Oliva, Alfonso
A1  - Klinger, Patricia
A1  - Kraus, Cornelia
A1  - Trautmann, Udo
A1  - Zenker, Martin
A1  - Zweier, Christiane
A1  - Wiesener, Antje
A1  - Jamra, Rami Abou
A1  - Kunstmann, Erdmute
A1  - Wieczorek, Dagmar
A1  - Uebe, Steffen
A1  - Ferrazzi, Fulvia
A1  - Büttner, Christian
A1  - Ekici, Arif B.
A1  - Rauch, Anita
A1  - Sticht, Heinrich
A1  - Dörr, Helmuth-Günther
A1  - Reis, André
A1  - Thiel, Christian T.
T1  - Clinical relevance of systematic phenotyping and exome sequencing in patients with short stature
JF  - Genetics in Medicine
N2  - Purpose
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.

Methods
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.

Results
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.

Conclusion
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.
KW  - growth
KW  - phenotypic spectrum
KW  - short stature
KW  - skeletal dysplasia
KW  - whole-exome sequencing
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227888
VL  - 20
ER  -