{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T16:58:58Z","timestamp":1773853138874,"version":"3.50.1"},"reference-count":24,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Subproject of the National Key R&amp;D Program","award":["2021YFC2701002"],"award-info":[{"award-number":["2021YFC2701002"]}]},{"name":"Subproject of the National Key R&amp;D Program","award":["82101796"],"award-info":[{"award-number":["82101796"]}]},{"name":"Subproject of the National Key R&amp;D Program","award":["81801461"],"award-info":[{"award-number":["81801461"]}]},{"name":"Subproject of the National Key R&amp;D Program","award":["81873836"],"award-info":[{"award-number":["81873836"]}]},{"name":"Subproject of the National Key R&amp;D Program","award":["81771594"],"award-info":[{"award-number":["81771594"]}]},{"name":"Subproject of the National Key R&amp;D Program","award":["81671474"],"award-info":[{"award-number":["81671474"]}]},{"name":"Subproject of the National Key R&amp;D Program","award":["81501267"],"award-info":[{"award-number":["81501267"]}]},{"name":"Subproject of the National Key R&amp;D Program","award":["2019A1515012034"],"award-info":[{"award-number":["2019A1515012034"]}]},{"name":"Subproject of the National Key R&amp;D Program","award":["202201020643"],"award-info":[{"award-number":["202201020643"]}]},{"name":"Subproject of the National Key R&amp;D Program","award":["20221A011029"],"award-info":[{"award-number":["20221A011029"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021YFC2701002"],"award-info":[{"award-number":["2021YFC2701002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82101796"],"award-info":[{"award-number":["82101796"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81801461"],"award-info":[{"award-number":["81801461"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873836"],"award-info":[{"award-number":["81873836"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771594"],"award-info":[{"award-number":["81771594"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81671474"],"award-info":[{"award-number":["81671474"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81501267"],"award-info":[{"award-number":["81501267"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2019A1515012034"],"award-info":[{"award-number":["2019A1515012034"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["202201020643"],"award-info":[{"award-number":["202201020643"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["20221A011029"],"award-info":[{"award-number":["20221A011029"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Guangdong Province","award":["2021YFC2701002"],"award-info":[{"award-number":["2021YFC2701002"]}]},{"name":"Natural Science Foundation of Guangdong Province","award":["82101796"],"award-info":[{"award-number":["82101796"]}]},{"name":"Natural Science Foundation of Guangdong Province","award":["81801461"],"award-info":[{"award-number":["81801461"]}]},{"name":"Natural Science Foundation of Guangdong Province","award":["81873836"],"award-info":[{"award-number":["81873836"]}]},{"name":"Natural Science Foundation of Guangdong Province","award":["81771594"],"award-info":[{"award-number":["81771594"]}]},{"name":"Natural Science Foundation of Guangdong Province","award":["81671474"],"award-info":[{"award-number":["81671474"]}]},{"name":"Natural Science Foundation of Guangdong Province","award":["81501267"],"award-info":[{"award-number":["81501267"]}]},{"name":"Natural Science Foundation of Guangdong Province","award":["2019A1515012034"],"award-info":[{"award-number":["2019A1515012034"]}]},{"name":"Natural Science Foundation of Guangdong Province","award":["202201020643"],"award-info":[{"award-number":["202201020643"]}]},{"name":"Natural Science Foundation of Guangdong Province","award":["20221A011029"],"award-info":[{"award-number":["20221A011029"]}]},{"name":"Project of Guangzhou Science and Technology Bureau","award":["2021YFC2701002"],"award-info":[{"award-number":["2021YFC2701002"]}]},{"name":"Project of Guangzhou Science and Technology Bureau","award":["82101796"],"award-info":[{"award-number":["82101796"]}]},{"name":"Project of Guangzhou Science and Technology Bureau","award":["81801461"],"award-info":[{"award-number":["81801461"]}]},{"name":"Project of Guangzhou Science and Technology Bureau","award":["81873836"],"award-info":[{"award-number":["81873836"]}]},{"name":"Project of Guangzhou Science and Technology Bureau","award":["81771594"],"award-info":[{"award-number":["81771594"]}]},{"name":"Project of Guangzhou Science and Technology Bureau","award":["81671474"],"award-info":[{"award-number":["81671474"]}]},{"name":"Project of Guangzhou Science and Technology Bureau","award":["81501267"],"award-info":[{"award-number":["81501267"]}]},{"name":"Project of Guangzhou Science and Technology Bureau","award":["2019A1515012034"],"award-info":[{"award-number":["2019A1515012034"]}]},{"name":"Project of Guangzhou Science and Technology Bureau","award":["202201020643"],"award-info":[{"award-number":["202201020643"]}]},{"name":"Project of Guangzhou Science and Technology Bureau","award":["20221A011029"],"award-info":[{"award-number":["20221A011029"]}]},{"name":"Project of Guangzhou Health Commission","award":["2021YFC2701002"],"award-info":[{"award-number":["2021YFC2701002"]}]},{"name":"Project of Guangzhou Health Commission","award":["82101796"],"award-info":[{"award-number":["82101796"]}]},{"name":"Project of Guangzhou Health Commission","award":["81801461"],"award-info":[{"award-number":["81801461"]}]},{"name":"Project of Guangzhou Health Commission","award":["81873836"],"award-info":[{"award-number":["81873836"]}]},{"name":"Project of Guangzhou Health Commission","award":["81771594"],"award-info":[{"award-number":["81771594"]}]},{"name":"Project of Guangzhou Health Commission","award":["81671474"],"award-info":[{"award-number":["81671474"]}]},{"name":"Project of Guangzhou Health Commission","award":["81501267"],"award-info":[{"award-number":["81501267"]}]},{"name":"Project of Guangzhou Health Commission","award":["2019A1515012034"],"award-info":[{"award-number":["2019A1515012034"]}]},{"name":"Project of Guangzhou Health Commission","award":["202201020643"],"award-info":[{"award-number":["202201020643"]}]},{"name":"Project of Guangzhou Health Commission","award":["20221A011029"],"award-info":[{"award-number":["20221A011029"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Objective: SHOX haploinsufficiency have been commonly found in isolated short stature (ISS) and L\u00e9ri\u2013Weill dyschondrosteosis (LWD) patients. However, few publications have described the genetic analysis and clinical characteristics of fetuses with SHOX haploinsufficiency. Methods: Chromosomal microarray (CMA) were applied in 14,051 fetuses and sequentially whole exome sequence (WES) in 1340 fetuses who underwent prenatal diagnosis during 2016\u20132021. The analysis and summary of molecular genetics, sonographic characteristics, and follow-up results were performed in fetuses with SHOX haploinsufficiency without other genetic etiologies. A comparison was made between three groups according to prenatal diagnostic indications. Results: 8 (0.06%) fetuses of SHOX haploinsufficiency were all detected by CMA, of which 5 (62.5%) were detected with short long bones by ultrasound scan, and 4 were inherited from their previously undiagnosed parents. No pathogenic SHOX variants were found by WES. The detection rate of SHOX haploinsufficiency was obviously higher in the short long bone group (2.6%, 5\/191) than the other abnormality group (0.03%, 1\/3919) or no ultrasound abnormality group (0.02%, 2\/9941). Three of the fetuses were liveborn with normal growth up to the age of four and four were terminated. Conclusion: The phenotype of fetuses with SHOX haploinsufficiency is highly varied. Over 1\/3 of the cases exhibited no phenotype and nearly 2\/3 with short long bones, in the absence of Madelung deformity during fetal development. SHOX haploinsufficiency should be considered in all antenatal presentations, especially in the case of isolated short long bones. CMA can provide effective detection.<\/jats:p>","DOI":"10.3390\/genes14010140","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T01:33:30Z","timestamp":1672882410000},"page":"140","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetic Analysis and Sonography Characteristics in Fetus with SHOX Haploinsufficiency"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9450-6376","authenticated-orcid":false,"given":"Lushan","family":"Li","sequence":"first","affiliation":[{"name":"Prenatal Diagnostic Center, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou 510620, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Fu","sequence":"additional","affiliation":[{"name":"Prenatal Diagnostic Center, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou 510620, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ru","family":"Li","sequence":"additional","affiliation":[{"name":"Eugenic and Perinatal Institute, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou 510620, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangyi","family":"Jing","sequence":"additional","affiliation":[{"name":"Eugenic and Perinatal Institute, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou 510620, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuxia","family":"Yu","sequence":"additional","affiliation":[{"name":"Eugenic and Perinatal Institute, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou 510620, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1233-5065","authenticated-orcid":false,"given":"Hang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Prenatal Diagnostic Center, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou 510620, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5405-1255","authenticated-orcid":false,"given":"You","family":"Wang","sequence":"additional","affiliation":[{"name":"Prenatal Diagnostic Center, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou 510620, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Yang","sequence":"additional","affiliation":[{"name":"Prenatal Diagnostic Center, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou 510620, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Pan","sequence":"additional","affiliation":[{"name":"Prenatal Diagnostic Center, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou 510620, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Han","sequence":"additional","affiliation":[{"name":"Prenatal Diagnostic Center, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou 510620, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhen","sequence":"additional","affiliation":[{"name":"Prenatal Diagnostic Center, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou 510620, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongzhi","family":"Li","sequence":"additional","affiliation":[{"name":"Prenatal Diagnostic Center, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou 510620, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Can","family":"Liao","sequence":"additional","affiliation":[{"name":"Prenatal Diagnostic Center, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University, Guangzhou 510620, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E1257","DOI":"10.1210\/jc.2011-3460","article-title":"Genotypes and Phenotypes of Children with SHOX Deficiency in France","volume":"97","author":"Rosilio","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1136\/jmg.2006.046581","article-title":"Genotypes and phenotypes in children with short stature: Clinical indicators of SHOX haploinsufficiency","volume":"44","author":"Rappold","year":"2007","journal-title":"J. Med. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"E11","DOI":"10.1136\/jmg.40.2.e11","article-title":"SHOX mutations detected by FISH and direct sequencing in patients with short stature","volume":"40","author":"Stuppia","year":"2003","journal-title":"J. Med. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/s41431-017-0080-4","article-title":"SHOX haploinsufficiency presenting with isolated short long bones in the second and third trimester","volume":"26","author":"Ramachandrappa","year":"2018","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.tjog.2017.01.006","article-title":"Molecular cytogenetic characterization and prenatal diagnosis of familial Xp22.33 microdeletion encompassing short stature homeobox gene in a male fetus with a favorable outcome","volume":"56","author":"Chen","year":"2017","journal-title":"Taiwan. J. Obstet. Gynecol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1111\/j.1471-0528.2002.01022.x","article-title":"Charts of fetal size: Limb bones","volume":"109","author":"Chitty","year":"2002","journal-title":"BJOG Int. J. Obstet. Gynaecol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1002\/uog.6252","article-title":"Fetal crown-rump length and estimation of gestational age in an ethnic Chinese population","volume":"33","author":"Sahota","year":"2009","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/uog.18915","article-title":"Whole exome sequencing as a diagnostic adjunct to clinical testing in fetuses with structural abnormalities","volume":"51","author":"Fu","year":"2018","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1159\/000444596","article-title":"SHOX Haploinsufficiency as a Cause of Syndromic and Nonsyndromic Short Stature","volume":"7","author":"Fukami","year":"2016","journal-title":"Mol. Syndromol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1002\/pd.5653","article-title":"Rapid prenatal diagnosis of skeletal dysplasia using medical trio exome sequencing: Benefit for prenatal counseling and pregnancy management","volume":"40","author":"Han","year":"2020","journal-title":"Prenat. Diagn."},{"key":"ref_12","first-page":"1430","article-title":"Rapid prenatal diagnosis using targeted exome sequencing: A cohort study to assess feasibility and potential impact on prenatal counseling and pregnancy management","volume":"20","author":"Chandler","year":"2018","journal-title":"Anesthesia Analg."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1210\/er.2016-1036","article-title":"A Track Record on SHOX: From Basic Research to Complex Models and Therapy","volume":"37","author":"Marchini","year":"2016","journal-title":"Endocr. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1159\/000324105","article-title":"Short Stature due to SHOX Deficiency: Genotype, Phenotype, and Therapy","volume":"75","author":"Binder","year":"2011","journal-title":"Horm. Res. Paediatr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1136\/jmg.38.1.1","article-title":"SHOX haploinsufficiency and overdosage: Impact of gonadal function status","volume":"38","author":"Ogata","year":"2001","journal-title":"J. Med. Genet."},{"key":"ref_16","first-page":"RA137-45","article-title":"Estrogen-like endocrine disrupting chemicals affecting puberty in humans\u2014A review","volume":"15","author":"Roy","year":"2009","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"977","DOI":"10.7863\/jum.1994.13.12.977","article-title":"Fetal biometry of skeletal dysplasias: A multicentric study","volume":"13","author":"Goncalves","year":"1994","journal-title":"J. Ultrasound Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1093\/hmg\/9.5.695","article-title":"The short stature homeobox gene SHOX is involved in skeletal abnormalities in Turner syndrome","volume":"9","author":"Schiller","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/sj.ejhg.5200402","article-title":"Phenotypic variation and genetic heterogeneity in L\u00e9ri-Weill syndrome","volume":"8","author":"Schiller","year":"2000","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_20","first-page":"551","article-title":"Analysis of short stature homeobox-containing gene ( SHOX ) and auxological phenotype in dyschondrosteosis and isolated Madelung deformity","volume":"109","author":"Grigelioniene","year":"2001","journal-title":"Qual. Life Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5674","DOI":"10.1210\/jcem.86.12.8125","article-title":"Phenotypes Associated with SHOX Deficiency","volume":"86","author":"Ross","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1210\/jc.2006-1409","article-title":"Growth hormone is effective in treatment of short stature associated with short stature homeobox-containing gene deficiency: Two-year results of a randomized, controlled, multicenter trial","volume":"92","author":"Blum","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"E1383","DOI":"10.1210\/jc.2013-1222","article-title":"GH treatment to final height produces similar height gains in patients with SHOX deficiency and Turner syndrome: Results of a multicenter trial","volume":"98","author":"Blum","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/S0749-0712(21)00229-8","article-title":"Madelung\u2019s deformity. Surgical correction through the anterior approach","volume":"16","author":"Carter","year":"2000","journal-title":"Hand Clin."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/1\/140\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T17:58:50Z","timestamp":1760119130000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/1\/140"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,4]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["genes14010140"],"URL":"https:\/\/doi.org\/10.3390\/genes14010140","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,4]]}}}