Journal article
Genotype-phenotype analysis of 523 patients by genetics evaluation and clinical exome sequencing
Pediatric research, Vol.87(4), pp.735-739
03/2020
DOI: 10.1038/s41390-019-0611-5
PMCID: PMC7082194
PMID: 31618753
Abstract
As clinical exome sequencing (CES) becomes more common, understanding which patients are most likely to benefit and in what manner is critical for the general pediatrics community to appreciate.
Five hundred and twenty-three patients referred to the Pediatric Genetics clinic at Michigan Medicine were systematically phenotyped by the presence or absence of abnormalities for 13 body/organ systems by a Clinical Genetics team. All patients then underwent CES.
Overall, 30% of patients who underwent CES had an identified pathogenic mutation. The most common phenotypes were developmental delay (83%), neuromuscular system abnormalities (81%), and multiple congenital anomalies (42%). In all, 67% of patients had a variant of uncertain significance (VUS) or gene of uncertain significance (GUS); 23% had no variants reported. There was a significant difference in the average number of body systems affected among these groups (pathogenic 5.89, VUS 6.0, GUS 6.12, and no variant 4.6; P < 0.00001). Representative cases highlight four ways in which CES is changing clinical pediatric practice.
Patients with identified variants are enriched for multiple organ system involvement. Furthermore, our phenotyping provides broad insights into which patients are most likely to benefit from genetics referral and CES and how those results can help guide clinical practice more generally.
Details
- Title: Subtitle
- Genotype-phenotype analysis of 523 patients by genetics evaluation and clinical exome sequencing
- Creators
- Mark N Ziats - University of Michigan–Ann ArborAyesha Ahmad - University of Michigan–Ann ArborJohn A Bernat - University of IowaRachel Fisher - University of Michigan–Ann ArborMegan Glassford - University of Michigan–Ann ArborMark C Hannibal - University of Michigan–Ann ArborJoseph E Jacher - University of Michigan–Ann ArborNatasha Weiser - University of Michigan–Ann ArborCatherine E Keegan - University of Michigan–Ann ArborKristen N Lee - University of Michigan–Ann ArborTessa B Marzulla - University of Michigan–Ann ArborBridget C O'Connor - University of Michigan–Ann ArborShane C Quinonez - University of Michigan–Ann ArborLauren Seemann - University of Michigan–Ann ArborLauren Turner - University of Michigan–Ann ArborStephanie Bielas - University of Michigan–Ann ArborNicholas L Harris - University of Michigan–Ann ArborJacob D Ogle - University of Michigan–Ann ArborJeffrey W Innis - University of Michigan–Ann ArborDonna M Martin - Children's Clinical Trial Support Unit, University of Michigan, Arbor, MI, USA. donnamm@umich.edu
- Resource Type
- Journal article
- Publication Details
- Pediatric research, Vol.87(4), pp.735-739
- DOI
- 10.1038/s41390-019-0611-5
- PMID
- 31618753
- PMCID
- PMC7082194
- ISSN
- 0031-3998
- eISSN
- 1530-0447
- Grant note
- R01 DC014456 / NIDCD NIH HHS R01 HD093570 / NICHD NIH HHS
- Language
- English
- Date published
- 03/2020
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984353842502771
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