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MRXSHG is a serious disorder with <jats:italic>CNKSR2<\/jats:italic> variant and at least 34 variants have been identified in MRXSHG patients. However, the genotype-phenotype correlation and variants characteristics of <jats:italic>CNKSR2<\/jats:italic> need further investigation and improvement.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>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 exon 15 from both the wild-type and the c.1658-3_1676del DNA sequences.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In this study, we reported two Chinese boys with MRXSHG and described some rare MRXSHG phenotypes, such as delayed bone age, slightly widened right fissure, and an underdeveloped right temporal lobe, characterized by reduced growth and volume compared to typical development. Two novel variants in <jats:italic>CNKSR2<\/jats:italic> (c.1658-3_1676del and c.1102G\u2009&gt;\u2009T, p.Gly368*) were identified in these cases. Minigenes results revealed that variant c.1658-3_1676del produced an aberrant spliceosome assembly.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We identified two novel <jats:italic>CNKSR2<\/jats:italic> variants in MRXSHG families, expanding the variant spectrum of <jats:italic>CNKSR2<\/jats:italic>, enriching MRXSHG-related phenotypes, and contributing to genetic counseling for MRXSHG patients.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s13052-025-01877-0","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T17:13:17Z","timestamp":1738948397000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification of Houge type of X-linked syndromic mental retardation caused by CNKSR2 truncated variants"],"prefix":"10.1186","volume":"51","author":[{"given":"Si-Hua","family":"Chang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie-Yuan","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Qiao","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Run-Yan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Xiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9956-5034","authenticated-orcid":false,"given":"Xia","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,2,7]]},"reference":[{"issue":"17","key":"1877_CR1","doi-asserted-by":"publisher","first-page":"11889","DOI":"10.1074\/jbc.274.17.11889","volume":"274","author":"I Yao","year":"1999","unstructured":"Yao I, Hata Y, Ide N, Hirao K, Deguchi M, Nishioka H, et al. 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All parents and patients provided informed consent for the collection of biological samples. Written consent was waived.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consents were obtained from the family members, and they consented to participation in this study and to information publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"31"}}