Format

Send to

Choose Destination
Genet Med. 2019 Jan;21(1):195-206. doi: 10.1038/s41436-018-0007-7. Epub 2018 Jun 18.

Targeted exome analysis identifies the genetic basis of disease in over 50% of patients with a wide range of ataxia-related phenotypes.

Author information

1
Department of Human Genetics, The University of Chicago, Chicago, IL, USA.
2
Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA.
3
Department of Neurology, Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
4
Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada.
5
The Ottawa Hospital/OHRI, Ottawa, ON, Canada.
6
Department of Neurology, The University of Chicago, Chicago, IL, USA.
7
Department of Human Genetics, The University of Chicago, Chicago, IL, USA. sdas@genetics.uchicago.edu.

Abstract

PURPOSE:

To examine the impact of a targeted exome approach for the molecular diagnosis of patients nationwide with a wide range of ataxia-related phenotypes.

METHODS:

One hundred and seventy patients with ataxia of unknown etiology referred from clinics throughout the United States and Canada were studied using a targeted exome approach. Patients ranged in age from 2 to 88 years. Analysis was focused on 441 curated genes associated with ataxia and ataxia-like conditions.

RESULTS:

Pathogenic and suspected diagnostic variants were identified in 88 of the 170 patients, providing a positive molecular diagnostic rate of 52%. Forty-six different genes were implicated, with the six most commonly mutated genes being SPG7, SYNE1, ADCK3, CACNA1A, ATP1A3, and SPTBN2, which accounted for >40% of the positive cases. In many cases a diagnosis was provided for conditions that were not suspected and resulted in the broadening of the clinical spectrum of several conditions.

CONCLUSION:

Exome sequencing with targeted analysis provides a high-yield approach for the genetic diagnosis of ataxia-related conditions. This is the largest targeted exome study performed to date in patients with ataxia and ataxia-like conditions and represents patients with a wide range of ataxia phenotypes typically encountered in neurology and genetics clinics.

KEYWORDS:

ataxia; clinical; diagnosis; exome sequencing; molecular genetics

PMID:
29915382
PMCID:
PMC6524765
[Available on 2020-01-01]
DOI:
10.1038/s41436-018-0007-7
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center