{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T11:03:16Z","timestamp":1756810996253,"version":"3.41.2"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T00:00:00Z","timestamp":1704412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>SHFM (Split Hand\/Foot Malformation) is a heterogeneous group of disorders characterized by the presence of clefts in the hands and feet, along with syndactyly of the digits. In this article, we describe a family in which two members exhibit characteristic developmental abnormalities associated with SHFM, presenting with variable clinical features. Using whole-genome sequencing, we identified a microduplication of a chromosomal segment on locus 10q24.32, specifically spanning positions 102934495 to 103496555, encompassing genes <jats:italic>BTRC<\/jats:italic>, <jats:italic>POLL<\/jats:italic>, <jats:italic>FBXW4<\/jats:italic> and <jats:italic>LBX1<\/jats:italic> in the proband. Genomic duplications, including these genes, were previously described in patients diagnosed with the third type of SHFM. We validated the presence of this structural rearrangement in 7 family members, including the proband and the proband\u2019s father. Remarkably, further investigation demonstrated that the detected duplication exhibits a mosaic state in the phenotypically normal paternal grandmother of the proband, thereby providing a plausible explanation for the absence of a pathological phenotype in her.<\/jats:p>","DOI":"10.3389\/fgene.2023.1303807","type":"journal-article","created":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T04:26:38Z","timestamp":1704428798000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Variable clinical presentation of split hand\/foot malformation syndrome in a family with microduplication of 10q24.32: a case report"],"prefix":"10.3389","volume":"14","author":[{"given":"Daria","family":"Akimova","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatiana","family":"Markova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Ampleeva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikhail","family":"Skoblov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1111\/j.1469-1809.1955.tb01281.x","article-title":"A possible case of delayed mutation in man","volume":"20","author":"Auerbach","year":"1956","journal-title":"Ann. Hum. Genet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1002\/ajmg.1320270319","article-title":"Apparently new autosomal recessive syndrome of mental retardation, distal limb deficiencies, oral involvement, and possible renal defect","volume":"27","author":"Buttiens","year":"1987","journal-title":"Am. J. Med. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1038\/s41467-023-37057-z","article-title":"Combinatorial effects on gene expression at the Lbx1\/Fgf8 locus resolve split-hand\/foot malformation type 3","volume":"14","author":"Cova","year":"2023","journal-title":"Nat. Commun."},{"key":"B4","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1186\/1471-2350-14-45","article-title":"Discontinuous microduplications at chromosome 10q24.31 identified in a Chinese family with split hand and foot malformation","volume":"14","author":"Dai","year":"2013","journal-title":"BMC Med. Genet."},{"key":"B5","first-page":"251","article-title":"Further evidence for germinal mosaicism in cleft hand\/cleft foot syndrome. Two affected halfsisters and normal father","volume":"12","author":"De Smet","year":"2001","journal-title":"Genet. Couns."},{"key":"B6","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1136\/jmg.2008.065888","article-title":"Distal limb deficiencies, micrognathia syndrome, and syndromic forms of split hand foot malformation (SHFM) are caused by chromosome 10q genomic rearrangements","volume":"47","author":"Dimitrov","year":"2010","journal-title":"J. Med. Genet."},{"key":"B7","doi-asserted-by":"publisher","first-page":"R51","DOI":"10.1093\/hmg\/ddg090","article-title":"Pathogenesis of split-hand\/split-foot malformation","volume":"1","author":"Duijf","year":"2003","journal-title":"Hum. Mol. Genet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1419","DOI":"10.1002\/ajmg.a.31244","article-title":"Genotype-phenotype correlations in mapped split hand foot malformation (SHFM) patients","volume":"140","author":"Elliott","year":"2006","journal-title":"Am. J. Med. Genet. A"},{"key":"B9","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1111\/j.1399-0004.2005.00530.x","article-title":"Split hand foot malformation (SHFM)","volume":"68","author":"Elliott","year":"2005","journal-title":"Clin. Genet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1007\/s00439-021-02295-y","article-title":"Genome sequencing in families with congenital limb malformations","volume":"140","author":"Elsner","year":"2021","journal-title":"Hum. Genet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1002\/ajmg.a.33942","article-title":"Somatic\/gonadal mosaicism in a syndromic form of ectrodactyly, including eye abnormalities, documented through array-based comparative genomic hybridization","author":"Filho","year":"2011","journal-title":"Am. J. Med. Genet. A"},{"key":"B12","doi-asserted-by":"publisher","first-page":"300060519879293","DOI":"10.1177\/0300060519879293","article-title":"Rare missense variant p.Ala505Ser in the ZAK protein observed in a patient with split-hand\/foot malformation from a non-consanguineous pedigree","volume":"48","author":"Funk","year":"2020","journal-title":"J. Int. Med. Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1177\/1753193418807375","article-title":"Insights into the pathogenesis and treatment of split\/hand foot malformation (cleft hand\/foot)","volume":"44","author":"Guero","year":"2019","journal-title":"J. Hand Surg. Eur."},{"key":"B14","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/s41431-018-0326-9","article-title":"Duplication of 10q24 locus: broadening the clinical and radiological spectrum","volume":"27","author":"Holder-Espinasse","year":"2019","journal-title":"Eur. J. Hum. Genet."},{"key":"B15","doi-asserted-by":"publisher","first-page":"19034","DOI":"10.1073\/pnas.0705483104","article-title":"Genetically regulated epigenetic transcriptional activation of retrotransposon insertion confers mouse dactylaplasia phenotype","volume":"104","author":"Kano","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e22533","DOI":"10.1097\/MD.0000000000022533","article-title":"The prenatal diagnosis and genetic counseling of chromosomal micro-duplication on 10q24.3 in a fetus: a case report and a brief review of the literature","volume":"99","author":"Lai","year":"2020","journal-title":"Med. Baltim."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2","DOI":"10.3390\/microarrays5010002","article-title":"Identification of critical region responsible for split hand\/foot malformation type 3 (SHFM3) phenotype through systematic review of literature and mapping of breakpoints using microarray data","volume":"5","author":"Li","year":"2015","journal-title":"Microarrays (Basel)"},{"key":"B18","doi-asserted-by":"publisher","first-page":"226","DOI":"10.2174\/1389202920666190530092856","article-title":"Split hand foot malformation syndrome: a novel heterozygous FGFR1 mutation detected by next generation sequencing","volume":"20","author":"Papasozomenou","year":"2019","journal-title":"Curr. Genomics"},{"key":"B19","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/s41439-023-00242-z","article-title":"A novel frameshift variant in UBA2 causing split-hand\/foot malformations in a Pakistani family","volume":"10","author":"Parveen","year":"2023","journal-title":"Hum. Genome Var."},{"key":"B20","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1111\/cge.14204","article-title":"Microduplication of BTRC detected in a Chinese family with split hand\/foot malformation type 3","volume":"102","author":"Qiu","year":"2022","journal-title":"Clin. Genet."},{"key":"B21","article-title":"Prevalence of rare diseases: bibliographic data","volume":"1","author":"Rath","year":"2022","journal-title":"Orphanet Rep. Ser."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1624","DOI":"10.1038\/s41436-021-01182-1","article-title":"UBA2 variants underlie a recognizable syndrome with variable aplasia cutis congenita and ectrodactyly","volume":"23","author":"Schnur","year":"2021","journal-title":"Genet. Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1007\/s13353-013-0178-5","article-title":"Split-hand\/foot malformation - molecular cause and implications in genetic counseling","volume":"55","author":"Sowinska-Seidler","year":"2014","journal-title":"J. Appl. Genet."},{"key":"B24","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1101\/gr.199430.115","article-title":"Exome sequencing and CRISPR\/Cas genome editing identify mutations of ZAK as a cause of limb defects in humans and mice","volume":"26","author":"Spielmann","year":"2016","journal-title":"Genome Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1159\/000453350","article-title":"A novel heterozygous intragenic sequence variant in DLX6 probably underlies first case of autosomal dominant split-hand\/foot malformation type 1","volume":"8","author":"Ullah","year":"2017","journal-title":"Mol. Syndromol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1159\/000502784","article-title":"Nonsyndromic split-hand\/foot malformation: recent classification","volume":"10","author":"Umair","year":"2020","journal-title":"Mol. Syndromol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1111\/cge.13152","article-title":"First direct evidence of involvement of a homozygous loss-of-function variant in the EPS15L1 gene underlying split-hand\/split-foot malformation","volume":"93","author":"Umair","year":"2018","journal-title":"Clin. Genet."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1303807\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T04:26:43Z","timestamp":1704428803000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2023.1303807\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,5]]},"references-count":27,"alternative-id":["10.3389\/fgene.2023.1303807"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2023.1303807","relation":{},"ISSN":["1664-8021"],"issn-type":[{"type":"electronic","value":"1664-8021"}],"subject":[],"published":{"date-parts":[[2024,1,5]]},"article-number":"1303807"}}