Diagnostic and cost utility of whole exome sequencing in peripheral neuropathy.

OBJECTIVE: To explore the diagnostic utility and cost effectiveness of whole exome sequencing (WES) in a cohort of individuals with peripheral neuropathy. METHODS: Singleton WES was performed in individuals recruited though one pediatric and one adult tertiary center between February 2014 and December 2015. Initial analysis was restricted to a virtual panel of 55 genes associated with peripheral neuropathies. Patients with uninformative results underwent expanded analysis of the WES data. Data on the cost of prior investigations and assessments performed for diagnostic purposes in each patient was collected. RESULTS: Fifty patients with a peripheral neuropathy were recruited (median age 18 years; range 2-68 years). The median time from initial presentation to study enrollment was 6 years 9 months (range 2 months-62 years), and the average cost of prior investigations and assessments for diagnostic purposes AU$4013 per patient. Eleven individuals received a diagnosis from the virtual panel. Eight individuals received a diagnosis following expanded analysis of the WES data, increasing the overall diagnostic yield to 38%. Two additional individuals were diagnosed with pathogenic copy number variants through SNP microarray. CONCLUSIONS: This study provides evidence that WES has a high diagnostic utility and is cost effective in patients with a peripheral neuropathy. Expanded analysis of WES data significantly improves the diagnostic yield in patients in whom a diagnosis is not found on the initial targeted analysis. This is primarily due to diagnosis of conditions caused by newly discovered genes and the resolution of complex and atypical phenotypes.

A longitudinal study of the Friedreich Ataxia Impact Scale.

BACKGROUND: Quality of life in Friedreich ataxia (FRDA) has been explored using various generic health status measurement tools, most commonly the Short Form Health Survey Version 2 (SF-36v2). The tool did not address many specific issues related to disease impact in people with FRDA. The Friedreich Ataxia Impact Scale (FAIS) was developed to examine clinically relevant areas in FRDA. The aims of the current study were to assess the relationship between the FAIS and clinical characteristics of FRDA, as well as to determine the responsiveness of the FAIS to change over one and two years. METHODS: One hundred and four individuals with FRDA, homozygous for the GAA expansion in intron 1 of FXN, completed the FAIS at baseline. Seventy individuals completed the FAIS again 12 months later and 49 completed the FAIS at 24 months. Clinical parameters and neurologic scales (Friedreich Ataxia Rating Scale (FARS)) were also recorded. RESULTS: The total FARS score, onset age and disease duration correlated significantly with FAIS subscales measuring symptoms and physical functioning. The physical and mental summary measures of the SF-36 V2 also correlated well with the FAIS subscales. Speech was the only subscale that demonstrated significant change over one and two years. CONCLUSIONS: The FAIS provides valuable insight into the perspective of individuals with FRDA on their health status, and is an important measure of morbidity. It has, however, limited responsiveness to change and its use in intervention studies is questionable.