Objective To analyze the phenotypes of a child with epilepsy and psychomotor development delay who carried CNTNAP2 gene variants.Methods The child,aged 5 years and 4 months,was admitted to our hospital's rehabilitation department due to delay in motor,language and cognition.The patient primarily presented with psychomotor retardation,epi-lepsy,ataxia and tendencies towards autism.Chromosomal microarray analysis(CMA)and trio-whole-exome sequencing(trio-WES)were performed on the child.Results The CMA resuls showed no abnormalities.Trio-WES identified two patho-genic compound heterozygous CNTNAP2(NM_014141.6)variants[c.451C＞T(p.Q151*)derived from her mother,c.3588_3591delGACA(N1198Pfs*21)derived from her father].These two CNTNAP2 variants are associated with Pitt-Hopkins-like syndrome 1.Sanger sequencing confirmed the findings of trio-WES.These two variants may damage the discoidin domain(also known as F5/8 C-domain)and laminin G-like 4 domain of CNTNAP2 protein,which may lead to sei-zures and psychomotor retardation.Conclusion Homozygous or compound heterozygous CNTNAP2 gene variants result in severe cognitive impairment,epilepsy,and behavioral abnormalities as main clinical manifestations.PTHSL1 has not been reported in China before this study,therefore this study reports two novel pathogenic CNTNAP2 gene variants that can assist clinicians in improving their ability for clinical diagnosis and genetic counseling.
维普
万方数据