Analysis of trio test in neurodevelopmental disorders

Abstract

BackgroundTrio test has been widely used for diagnosis of various hereditary disorders. We aimed to investigate the contribution of trio test in genetically diagnosing neurodevelopmental disorders (NDD).MethodsWe retrospectively reviewed 2,059 NDD cases with genetic test results. The trio test was conducted in 563 cases. Clinical usefulness, optimal timing, and methods for the trio test were reviewed.ResultsPathogenic or likely pathogenic variants were detected in 112 of 563 (19.9%) patients who underwent the trio test. With trio test results, the overall diagnostic yield increased by 5.4% (112/2,059). Of 165 de novo variants detected, 149 were pathogenic and we detected 85 novel pathogenic variants. Pathogenic, de novo variants were frequently detected in CDKL5, ATP1A3, and STXBP1.ConclusionThe trio test is an efficient method for genetically diagnosing NDD. We identified specific situations where a certain trio test is more appropriate, thereby providing a guide for clinicians when confronted with variants of unknown significance of specific genes.

Unusual Voltage-Gated Sodium and Potassium Channelopathies Related to Epilepsy

“… 18 19 20 The patients carrying the c.1106G>T and c.1237G>A variants were reported previously by our institution. 17 The c.916>T variant was located in the S4 segment, whereas the other pathogenic variants were located between segments S5 and S6 ( Fig. 2 ).…”

“…The other two patients with KCNA2 missense variants, reported previously by our institution, showed generalized tonic or tonic–clonic seizures. 17 Their EEG findings showed focal epileptiform discharges. One of the patients showed developmental delay and an ataxic gait.…”

“…The c.785C>T and c.1130A>G variants were reported previously by our institution, but not their specific clinical characteristics. 17 The probands were diagnosed with focal epilepsy but manifested with generalized seizures. The proband with the c.785C>T variant also exhibited developmental delay and an ataxic gait.…”