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Wolf-Hirschhorn syndrome patients exhibit characteristic facial dysmorphism, growth retardation, developmental delay, intellectual disability and seizure disorders. Recently, <jats:italic>NSD2<\/jats:italic> gene located within the 165\u2009kb Wolf-Hirschhorn syndrome critical region was identified as the key causal gene responsible for most if not all phenotypes of Wolf-Hirschhorn syndrome. So far, eight <jats:italic>NSD2<\/jats:italic> loss of function variants have been reported in patients from different parts of the world, all were de novo variants.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>In our study, we performed whole exome sequencing for two patients from one family. We also reviewed more <jats:italic>NSD2<\/jats:italic> mutation cases in pervious literature.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>A novel loss of function <jats:italic>NSD2<\/jats:italic> variant, c.1577dupG (p.Asn527Lysfs*14), was identified in a Chinese family in the proband and her father both affected with intellectual disability. After reviewing more <jats:italic>NSD2<\/jats:italic> mutation cases in pervious literature, we found none of them had facial features that can be recognized as Wolf-Hirschhorn syndrome. In addition, we have given our proband growth hormone and followed up with this family for 7.5\u2009years.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Here we reported the first familial <jats:italic>NSD2<\/jats:italic> variant and the long-term effect of growth hormone therapy for patients. Our results suggested <jats:italic>NSD2<\/jats:italic> mutation might cause a distinct intellectual disability and short stature syndrome.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12920-020-00831-9","type":"journal-article","created":{"date-parts":[[2020,12,4]],"date-time":"2020-12-04T12:04:34Z","timestamp":1607083474000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The first familial NSD2 cases with a novel variant in a Chinese father and daughter with atypical WHS facial features and a 7.5-year follow-up of growth hormone therapy"],"prefix":"10.1186","volume":"13","author":[{"given":"Xuyun","family":"Hu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuchuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liya","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miao","family":"Qin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongdou","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengting","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaoke","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunxiu","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5820-0839","authenticated-orcid":false,"given":"Yiping","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,12,4]]},"reference":[{"issue":"3","key":"831_CR1","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1002\/ajmg.c.31449","volume":"169","author":"A Battaglia","year":"2015","unstructured":"Battaglia A, Carey JC, South ST. 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Written approvals, based on informed consent, for the diagnostic tests and genetic analysis were given by the patients or their parents in accordance with the Declaration of Helsinki. Written informed consents to participate were obtained from participants and the parents of the participant under the age of 16.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consents for publication of clinical details and clinical images were obtained from participants and the parents of the participant under the age of 16.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"181"}}