Ataxia

Teams of 3–4 physicians were assigned 1–4 CD-related terms. Each team first carried out a literature search (Table 1). We searched the entire electronic database PubMed up to January 2011 using the terms of this review as key words. These included: Coeliac disease and these descriptors of CD: asymptomatic, atypical, classical, latent, non-classical, overt, paediatric classical, potential, refractory, silent, subclinical, symptomatic, typical, CD serology, CD autoimmunity, genetically at risk of CD, dermatitis herpetiformis, gluten, gluten ataxia, gluten intolerance, gluten sensitivity, and gliadin-specific antibodies.We restricted most of our review to original papers and reviews. Most papers had been published after 1990. The teams then suggested definitions for each term.

There were 2000 consecutive, unrelated patient cases in this study who were referred from physicians starting in June 2012 through November 2013 for clinical whole-exome sequencing at the Whole Genome Laboratory of Baylor College of Medicine. The laboratory has been certified by both the College of American Pathologists and the US Centers for Disease Control and Prevention Clinical Laboratory Improvement Amendments of 1988. A request for whole-exome sequencing testing was made solely at the discretion of the referring physician with no inclusion or exclusion criteria and no filtering by the laboratory.^{10 (link)} The only reason for the laboratory to decline testing was for financial reasons (eg, denial of coverage by insurance). Representative clinical cases are presented in Table 1 as examples of prior diagnostic evaluations for patients referred for whole-exome sequencing. These examples were selected based on verification of completeness of prior laboratory testing and for demonstration of possible outcomes of whole-exome sequencing (total cost for laboratory testing for case No. 218 appears in eTable 1 in the Supplement). The initial 250 cases previously reported were excluded.^{1 (link)} Requisition and consent forms are available at https://www.bcm.edu/geneticlabs/.
Peripheral blood, tissue, or extracted DNA samples were collected from patients or their parents and submitted with a requisition form, which included informed consent and patient clinical data as previously described.^{1 (link)} Following pretest counseling for whole-exome sequencing, patients and parents/ guardians were given options of not receiving specific categories of results (detailed later). The phenotypes of the 2000 patients were categorized into 4 groups at the time of whole-exome sequencing data analysis according to the clinical data provided by the referring physician (Table 2 and eTable 2 in the Supplement).
The neurological group consisted of patients with findings confined to neurological or developmental systems (eg, developmental delay, intellectual disability, autism, speech delay). The neurological plus other organ systems group included findings listed for the neurological group plus at least 1 finding from another organ system, which could include renal, cardiac, gastrointestinal, pulmonary, or multiple congenital anomalies. The specific neurological group included more defined neurological signs and symptoms (eg, ataxia, movement disorder, spastic paraplegia) than the neurological group. The nonneurological group had findings from organ systems other than neurological. The 4 groups were developed by clinical geneticists and medical directors of the laboratory and assignments were made by the laboratory directors at the time of case review and before the results of whole-exome sequencing were known. For cases with complex, overlapping features, consultation with the medical director was performed.
This analysis of deidentified patient data and aggregate clinical genomics data was approved by the institutional review board at Baylor College of Medicine.