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Eur J Hum Genet. 2017 Feb;25(2):176-182. doi: 10.1038/ejhg.2016.146. Epub 2016 Nov 16.

Clinical exome sequencing: results from 2819 samples reflecting 1000 families.

Author information

1
Centogene AG, Rostock, Germany.
2
Division of Genetics, Department of Pediatrics, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
3
College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
4
Division of Neurology, Department of Pediatrics, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
5
Department of pathology, King Abdulaziz Medical City, Riyadh, Saudi Arabia.
6
Division of Metabolic and Genetics, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
7
Division of Pediatrics, Johns Hopkins Aramco hospital, Dhahran Health Center, Saudi Aramco, Dhahran, Saudi Arabia.
8
Albrecht-Kossel-Institute for Neuroregeneration, Medical University Rostock, Rostock, Germany.
9
Institute of Human Genetics, University of Leipzig Hospitals and Clinics, Leipzig, Germany.

Abstract

We report our results of 1000 diagnostic WES cases based on 2819 sequenced samples from 54 countries with a wide phenotypic spectrum. Clinical information given by the requesting physicians was translated to HPO terms. WES processes were performed according to standardized settings. We identified the underlying pathogenic or likely pathogenic variants in 307 families (30.7%). In further 253 families (25.3%) a variant of unknown significance, possibly explaining the clinical symptoms of the index patient was identified. WES enabled timely diagnosing of genetic diseases, validation of causality of specific genetic disorders of PTPN23, KCTD3, SCN3A, PPOX, FRMPD4, and SCN1B, and setting dual diagnoses by detecting two causative variants in distinct genes in the same patient. We observed a better diagnostic yield in consanguineous families, in severe and in syndromic phenotypes. Our results suggest that WES has a better yield in patients that present with several symptoms, rather than an isolated abnormality. We also validate the clinical benefit of WES as an effective diagnostic tool, particularly in nonspecific or heterogeneous phenotypes. We recommend WES as a first-line diagnostic in all cases without a clear differential diagnosis, to facilitate personal medical care.

PMID:
27848944
PMCID:
PMC5255946
DOI:
10.1038/ejhg.2016.146
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

DT, AMBA, MERW, JK, KKK, AM, OP, MCdC, CB, KW, RS, JMGA, OB, SK, NN, MW, RAJ are employed at Centogene AG; AR has financial holdings in Centogene AG; WE, MTAR, AAR, WAT, AAlo, MAB, and MA are employees at King Abdulaziz Medical city; AAlh is employee at Prince Sultan Military Medical City; NAS is employee at Johns Hopkins Aramco hospital.

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