2p25.3 microduplications involving MYT1L: further phenotypic characterization through an assessment of 15 new cases and a literature review

Abstract

AbstractMicroduplications involving theMYT1Lgene have mostly been described in series of patients with isolated schizophrenia. However, few reports have been published, and the phenotype has still not been well characterized. We sought to further characterize the phenotypic spectrum of this condition by describing the clinical features of patients with a pure 2p25.3 microduplication that included all or part ofMYT1L. Through a French national collaboration and a literature review, we assessed a large cohort of patients (n = 43) with pure 2p25.3 microduplications identified by chromosomal microarray analysis. For each case, we recorded clinical data, the microduplication size, and the inheritance pattern. The clinical features were variable and included developmental and speech delays (33%), autism spectrum disorder (23%), mild-to-moderate intellectual disability (21%), schizophrenia (21%), or behavioral disorders (16%). Eleven patients did not have an obvious neuropsychiatric disorder. The microduplications ranged from 62.4 kb to 3.8 Mb in size and led to either duplication of all or part ofMYT1L. There were seven cases of intragenic duplication. The inheritance pattern was available for 18 patients: the microduplication was inherited in 13 cases, and all but one of the parents had a normal phenotype. Our comprehensive review and expansion of the phenotypic spectrum associated with 2p25.3 microduplications involvingMYT1L(previously linked to schizophrenia) should help clinicians to better assess, counsel and manage affected individuals.MYT1Lmicroduplications are characterized by a spectrum of neuropsychiatric phenotypes with incomplete penetrance and variable expressivity, which are probably due to as-yet unknown genetic and nongenetic modifiers.