biostudies-literatureChang SHKey Research and Development Program of Liaoning ProvinceNatural Science Foundation of Hunan ProvinceNatural Science Project of Changsha CityYouth Science Foundation of Xiangya HospitalNational Natural Science Foundation of China31https://www.ebi.ac.uk/biostudies/studies/S-EPMC11806549biostudies-literatureUnknown51(1)<h4>Background</h4>Houge type of X-linked syndromic mental retardation (MRXSHG) is a type of X-linked condition which is mainly manifested as delayed development, mental retardation, epilepsy that begins at an early age, and delayed language acquisition. MRXSHG is a serious disorder with CNKSR2 variant and at least 34 variants have been identified in MRXSHG patients. However, the genotype-phenotype correlation and variants characteristics of CNKSR2 need further investigation and improvement.<h4>Methods</h4>Two Chinese MRXSHG families were recruited, and their genetic causes were investigated using whole-exome sequencing (WES), Sanger sequencing, and bioinformatics analysis. To verify the impact of these variants, we used real-time PCR and minigenes consisting of exon 14, intron 14, and exoItalian journal of pediatricsIdentification of Houge type of X-linked syndromic mental retardation caused by CNKSR2 truncated variants.PMC11806549821705982022sk20342024JJ66932022JJ300582022Q10kq22021172022JJ30967Jin JYXiang RWang RYHu YQChang SHWang XfalseIdentification of Houge type of X-linked syndromic mental retardation caused by CNKSR2 truncated variants.<h4>Background</h4>Houge type of X-linked syndromic mental retardation (MRXSHG) is a type of X-linked condition which is mainly manifested as delayed development, mental retardation, epilepsy that begins at an early age, and delayed language acquisition. MRXSHG is a serious disorder with CNKSR2 variant and at least 34 variants have been identified in MRXSHG patients. However, the genotype-phenotype correlation and variants characteristics of CNKSR2 need further investigation and improvement.<h4>Methods</h4>Two Chinese MRXSHG families were recruited, and their genetic causes were investigated using whole-exome sequencing (WES), Sanger sequencing, and bioinformatics analysis. To verify the impact of these variants, we used real-time PCR and minigenes consisting of exon 14, intron 14, and exo2025-01-01T00:00:00Z2025 Feb2026-06-01T05:02:33.382Z2025-04-04T13:11:24.11ZS-EPMC118065493992070810.1186/s13052-025-01877-0