{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:43:48Z","timestamp":1787028228002,"version":"build-2736575974"},"reference-count":98,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T00:00:00Z","timestamp":1625702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R03HD099516"],"award-info":[{"award-number":["R03HD099516"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Arthrogryposis multiplex congenita (AMC) describes a group of conditions characterized by the presence of non-progressive congenital contractures in multiple body areas. Scoliosis, defined as a coronal plane spine curvature of \u226510 degrees as measured radiographically, has been reported to occur in approximately 20% of children with AMC. To identify genes that are associated with both scoliosis as a clinical outcome and AMC, we first queried the DECIPHER database for copy number variations (CNVs). Upon query, we identified only two patients with both AMC and scoliosis (AMC-SC). The first patient contained CNVs in three genes (FBN2, MGF10, and PITX1), while the second case had a CNV in ZC4H2. Looking into small variants, using a combination of Human Phenotype Ontogeny and literature searching, 908 genes linked with scoliosis and 444 genes linked with AMC were identified. From these lists, 227 genes were associated with AMC-SC. Ingenuity Pathway Analysis (IPA) was performed on the final gene list to gain insight into the functional interactions of genes and various categories. To summarize, this group of genes encompasses a diverse group of cellular functions including transcription regulation, transmembrane receptor, growth factor, and ion channels. These results provide a focal point for further research using genomics and animal models to facilitate the identification of prognostic factors and therapeutic targets for AMC.<\/jats:p>","DOI":"10.3390\/genes12071052","type":"journal-article","created":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T10:42:17Z","timestamp":1625740937000},"page":"1052","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A Genomic Approach to Delineating the Occurrence of Scoliosis in Arthrogryposis Multiplex Congenita"],"prefix":"10.3390","volume":"12","author":[{"given":"Xenia","family":"Latypova","sequence":"first","affiliation":[{"name":"Grenoble Institut Neurosciences, Universit\u00e9 Grenoble Alpes, Inserm, U1216, CHU Grenoble Alpes, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan Giovanni","family":"Creadore","sequence":"additional","affiliation":[{"name":"Shriners Hospitals for Children Headquarters, Tampa, FL 33607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00e9mi","family":"Dahan-Oliel","sequence":"additional","affiliation":[{"name":"Shriners Hospitals for Children, Montreal, QC H4A 0A9, Canada"},{"name":"School of Physical & Occupational Therapy, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 2M1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anxhela Gjyshi","family":"Gustafson","sequence":"additional","affiliation":[{"name":"Shriners Hospitals for Children Headquarters, Tampa, FL 33607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Wei-Hung Hwang","sequence":"additional","affiliation":[{"name":"Shriners Hospitals for Children, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Bedard","sequence":"additional","affiliation":[{"name":"Alberta Congenital Anomalies Surveillance System, Alberta Health Services, Edmonton, AB T5J 3E4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamran","family":"Shazand","sequence":"additional","affiliation":[{"name":"Shriners Hospitals for Children Headquarters, Tampa, FL 33607, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4033-6540","authenticated-orcid":false,"given":"Harold J. 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J. Med. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1159\/000446617","article-title":"Arthrogryposis as a Syndrome: Gene Ontology Analysis","volume":"7","author":"Hall","year":"2016","journal-title":"Mol. Syndr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1002\/ajmg.c.31733","article-title":"Gene ontology analysis of arthrogryposis (multiple congenital contractures)","volume":"181","author":"Kiefer","year":"2019","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"40","DOI":"10.2106\/JBJS.I.00281","article-title":"Arthrogryposis: A Review and Update","volume":"91","author":"Bamshad","year":"2009","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1002\/ajmg.c.31716","article-title":"Classification of arthrogryposis","volume":"181","author":"Hall","year":"2019","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1002\/ajmg.a.36395","article-title":"Amyoplasia revisited","volume":"164","author":"Hall","year":"2014","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1097\/00007632-197806000-00009","article-title":"Scoliosis in Arthrogryposis Multiplex Congenita","volume":"3","author":"Drummond","year":"1978","journal-title":"Spine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"293","DOI":"10.2106\/00004623-197860030-00003","article-title":"Scoliosis in arthrogryposis multiplex congenita","volume":"60","author":"Herron","year":"1978","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"S24","DOI":"10.1097\/BPO.0000000000000993","article-title":"Treatment of Scoliosis Associated with Arthrogryposis Multiplex Congenita","volume":"37","author":"Komolkin","year":"2017","journal-title":"J. Pediatr. Orthop."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1097\/01241398-200009000-00021","article-title":"Scoliosis in arthrogryposis multiplex congenita: Results after nonsurgical and surgical treatment","volume":"20","author":"Yingsakmongkol","year":"2000","journal-title":"J. Pediatr. Orthop."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"15030","DOI":"10.1038\/nrdp.2015.30","article-title":"Adolescent idiopathic scoliosis","volume":"1","author":"Cheng","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"115563","DOI":"10.1016\/j.bone.2020.115563","article-title":"From genetics to epigenetics to unravel the etiology of adolescent idiopathic scoliosis","volume":"140","author":"Bas","year":"2020","journal-title":"Bone"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1111\/cge.13798","article-title":"Early-onset nucleotide excision repair disorders with neurological impairment: Clues for early diagnosis and prognostic counseling","volume":"98","author":"Baer","year":"2020","journal-title":"Clin. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1016\/j.bbamcr.2009.09.004","article-title":"SPFH1 and SPFH2 mediate the ubiquitination and degradation of inositol 1,4,5-trisphosphate receptors in muscarinic receptor-expressing HeLa cells","volume":"1793","author":"Wang","year":"2009","journal-title":"Biochim. Biophys. Acta BBA Bioenerg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1073\/pnas.96.5.2305","article-title":"Mutations in the nebulin gene associated with autosomal recessive nemaline myopathy","volume":"96","author":"Pelin","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1002\/humu.21059","article-title":"Mutations and polymorphisms of the skeletal muscle alpha-actin gene (ACTA1)","volume":"30","author":"Laing","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"51208","DOI":"10.1074\/jbc.M409036200","article-title":"Discovery and characterization of a novel, widely expressed metalloprotease, ADAMTS10, and its proteolytic activation","volume":"279","author":"Somerville","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1038\/ng.2765","article-title":"Mutations in genes encoding the cadherin receptor-ligand pair DCHS1 and FAT4 disrupt cerebral cortical development","volume":"45","author":"Cappello","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1002\/humu.21636","article-title":"Sixteen years and counting: The current understanding of fibroblast growth factor receptor 3 (FGFR3) signaling in skeletal dysplasias","volume":"33","author":"Wilcox","year":"2012","journal-title":"Hum. Mutat."},{"key":"ref_20","first-page":"1","article-title":"Missense Mutations in GDF-5 Signaling: Molecular Mechanisms behind Skeletal Malformation","volume":"Volume 1","author":"David","year":"2012","journal-title":"Mutations in Human Genetic Disease"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.bbrc.2004.10.055","article-title":"Cartilage-derived morphogenetic protein-1 promotes the differentiation of mesenchymal stem cells into chondrocytes","volume":"325","author":"Bai","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.ejmg.2017.03.014","article-title":"Fetal costello syndrome with neuromuscular spindles excess and p.Gly12Val HRAS mutation","volume":"60","author":"Loget","year":"2017","journal-title":"Eur. J. Med. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1086\/301936","article-title":"Mutations in the human sterol delta7-reductase gene at 11q12-13 cause Smith-Lemli-Opitz syndrome","volume":"63","author":"Wassif","year":"1998","journal-title":"Am. J. Hum. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/ng0197-70","article-title":"UBE3A\/E6-AP mutations cause Angelman syndrome","volume":"15","author":"Kishino","year":"1997","journal-title":"Nat. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.1073\/pnas.96.6.2919","article-title":"Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations","volume":"96","author":"Basson","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.devcel.2009.11.013","article-title":"Tbx4 and Tbx5 Acting in Connective Tissue Are Required for Limb Muscle and Tendon Patterning","volume":"18","author":"Hasson","year":"2010","journal-title":"Dev. Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1093\/hmg\/ddw033","article-title":"The transcription coactivator ASC-1 is a regulator of skeletal myogenesis, and its deficiency causes a novel form of congenital muscle disease","volume":"25","author":"Davignon","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1001\/archneur.60.4.598","article-title":"Phenotypical Features of a Moroccan Family With Autosomal Recessive Charcot-Marie-Tooth Disease Associated With the S194X Mutation in the GDAP1 Gene","volume":"60","author":"Birouk","year":"2003","journal-title":"Arch. Neurol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1007\/s10038-008-0249-3","article-title":"A novel GDAP1 Q218E mutation in autosomal dominant Charcot-Marie-Tooth disease","volume":"53","author":"Chung","year":"2008","journal-title":"J. Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1212\/01.WNL.0000036272.36047.54","article-title":"Mutations in GDAP1: Autosomal recessive CMT with demyelination and axonopathy","volume":"59","author":"Nelis","year":"2002","journal-title":"Neurology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/ng796","article-title":"Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot-Marie-Tooth disease type 4A\/8q21","volume":"30","author":"Baxter","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/ng798","article-title":"The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease","volume":"30","author":"Cuesta","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0092-8674(01)00205-7","article-title":"Mutations in the RNA Component of RNase MRP Cause a Pleiotropic Human Disease, Cartilage-Hair Hypoplasia","volume":"104","author":"Pelin","year":"2001","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Rosenbluh, J., Nijhawan, D., Chen, Z., Wong, K.-K., Masutomi, K., and Hahn, W.C. (2011). RMRP Is a Non-Coding RNA Essential for Early Murine Development. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0026270"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1086\/506256","article-title":"Mutations in the Embryonal Subunit of the Acetylcholine Receptor (CHRNG) Cause Lethal and Escobar Variants of Multiple Pterygium Syndrome","volume":"79","author":"Morgan","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/j.ajhg.2014.03.015","article-title":"Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5","volume":"94","author":"McMillin","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1126\/science.1065521","article-title":"ATR and ATRIP: Partners in Checkpoint Signaling","volume":"294","author":"Cortez","year":"2001","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1002\/humu.22245","article-title":"Primary microcephaly, impaired DNA replication, and genomic instability caused by compound heterozygous ATR mutations","volume":"34","author":"Gaillard","year":"2013","journal-title":"Hum. Mutat."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"12956","DOI":"10.1073\/pnas.0502562102","article-title":"Central IL-1 receptor signaling regulates bone growth and mass","volume":"102","author":"Bajayo","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/j.ajhg.2016.05.024","article-title":"Mutations in MAP3K7 that Alter the Activity of the TAK1 Signaling Complex Cause Frontometaphyseal Dysplasia","volume":"99","author":"Wade","year":"2016","journal-title":"Am. J. Hum. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1038\/ncb891","article-title":"Bicaudal-D regulates COPI-independent Golgi\u2013ER transport by recruiting the dynein\u2013dynactin motor complex","volume":"4","author":"Matanis","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.ajhg.2013.04.018","article-title":"Mutations in BICD2 Cause Dominant Congenital Spinal Muscular Atrophy and Hereditary Spastic Paraplegia","volume":"92","author":"Oates","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/ng.2007.65","article-title":"Mutations in mRNA export mediator GLE1 result in a fetal motoneuron disease","volume":"40","author":"Nousiainen","year":"2008","journal-title":"Nat. Genet."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1002\/humu.23599","article-title":"LAMA2gene mutation update: Toward a more comprehensive picture of the laminin-\u03b12 variome and its related phenotypes","volume":"39","author":"Oliveira","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1750-1172-4-11","article-title":"Sheldon-Hall syndrome","volume":"4","author":"Toydemir","year":"2009","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.ejmg.2014.08.007","article-title":"A syndromic form of Pierre Robin sequence is caused by 5q23 deletions encompassing FBN2 and PHAX","volume":"57","author":"Ansari","year":"2014","journal-title":"Eur. J. Med. Genet."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Huang, N., Lee, I., Marcotte, E.M., and Hurles, M.E. (2010). Characterising and Predicting Haploinsufficiency in the Human Genome. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1001154"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1002\/humu.20854","article-title":"Comprehensive clinical and molecular assessment of 32 probands with congenital contractural arachnodactyly: Report of 14 novel mutations and review of the literature","volume":"30","author":"Callewaert","year":"2009","journal-title":"Hum. Mutat."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1136\/jmedgenet-2018-105793","article-title":"H2AFY promoter deletion causes PITX1 endoactivation and Liebenberg syndrome","volume":"56","author":"Kragesteen","year":"2019","journal-title":"J. Med. Genet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1002\/humu.23841","article-title":"Deleterious de novo variants of X-linked ZC4H2 in females cause a variable phenotype with neurogenic arthrogryposis multiplex congenita","volume":"40","author":"Frints","year":"2019","journal-title":"Hum. Mutat."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1091\/mbc.E18-08-0526","article-title":"Reductions in ATPase activity, actin sliding velocity, and myofibril stability yield muscle dysfunction in Drosophila models of myosin-based Freeman\u2013Sheldon syndrome","volume":"30","author":"Rao","year":"2019","journal-title":"Mol. Biol. Cell"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1136\/jmedgenet-2015-103620","article-title":"Deficiency of the myogenic factor MyoD causes a perinatally lethal fetal akinesia","volume":"53","author":"Watson","year":"2016","journal-title":"J. Med. Genet."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.devcel.2013.12.020","article-title":"Gene Regulatory Networks and Transcriptional Mechanisms that Control Myogenesis","volume":"28","author":"Buckingham","year":"2014","journal-title":"Dev. Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.devcel.2015.05.009","article-title":"A Long Non-coding RNA, LncMyoD, Regulates Skeletal Muscle Differentiation by Blocking IMP2-Mediated mRNA Translation","volume":"34","author":"Gong","year":"2015","journal-title":"Dev. Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1038\/ng1629","article-title":"Epimutation of the telomeric imprinting center region on chromosome 11p15 in Silver-Russell syndrome","volume":"37","author":"Gicquel","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1210\/jc.2008-1805","article-title":"Clinically Distinct Epigenetic Subgroups in Silver-Russell Syndrome: The Degree ofH19Hypomethylation Associates with Phenotype Severity and Genital and Skeletal Anomalies","volume":"94","author":"Bruce","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_57","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Mirzaa, G., and Amemiya, A. (1993). Silver-Russell Syndrome. GeneReviews\u00ae, University of Washington."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/s41436-019-0609-8","article-title":"A clinical scoring system for congenital contractural arachnodactyly","volume":"22","author":"Meerschaut","year":"2020","journal-title":"Genet. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3943","DOI":"10.1093\/hmg\/ddr313","article-title":"Pitx1 haploinsufficiency causes clubfoot in humans and a clubfoot-like phenotype in mice","volume":"20","author":"Alvarado","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.ajhg.2013.03.021","article-title":"ZC4H2 Mutations Are Associated with Arthrogryposis Multiplex Congenita and Intellectual Disability through Impairment of Central and Peripheral Synaptic Plasticity","volume":"92","author":"Hirata","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4848","DOI":"10.1093\/hmg\/ddv208","article-title":"ZC4H2, an XLID gene, is required for the generation of a specific subset of CNS interneurons","volume":"24","author":"May","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1002\/ajmg.a.38155","article-title":"ZC4H2 deletions can cause severe phenotype in female carriers","volume":"173","author":"Zanzottera","year":"2017","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1136\/jmedgenet-2011-100378","article-title":"CHRNG genotype-phenotype correlations in the multiple pterygium syndromes","volume":"49","author":"Vogt","year":"2012","journal-title":"J. Med. Genet."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1093\/hmg\/ddp587","article-title":"Myosin binding protein C1: A novel gene for autosomal dominant distal arthrogryposis type 1","volume":"19","author":"Gurnett","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"4967","DOI":"10.1093\/hmg\/ddt344","article-title":"MYBPC1 mutations impair skeletal muscle function in zebrafish models of arthrogryposis","volume":"22","author":"Ha","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1016\/j.ajhg.2018.04.008","article-title":"Recessive Spondylocarpotarsal Synostosis Syndrome Due to Compound Heterozygosity for Variants in MYH3","volume":"102","author":"Wells","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/j.ajhg.2015.04.004","article-title":"Autosomal-Dominant Multiple Pterygium Syndrome Is Caused by Mutations in MYH3","volume":"96","author":"Chong","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e12356","DOI":"10.15252\/emmm.202012356","article-title":"MYH 3-associated distal arthrogryposis zebrafish model is normalized with para-aminoblebbistatin","volume":"12","author":"Whittle","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Zhu, X., Wang, F., Zhao, Y., Yang, P., Chen, J., Sun, H., Liu, L., Li, W., Pan, L., and Guo, Y. (2014). A Gain-of-Function Mutation in Tnni2 Impeded Bone Development through Increasing Hif3a Expression in DA2B Mice. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004589"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.lfs.2018.04.021","article-title":"The protective effect of Hif3a RNA interference and HIF-prolyl hydroxylase inhibition on cardiomyocytes under anoxia-reoxygenation","volume":"202","author":"Drevytska","year":"2018","journal-title":"Life Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/ajmg.c.31718","article-title":"Disease coding systems for arthrogryposis multiplex congenita","volume":"181","author":"Bedard","year":"2019","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"D1207","DOI":"10.1093\/nar\/gkaa1043","article-title":"The Human Phenotype Ontology in 2021","volume":"49","author":"Gargano","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/s41436-019-0680-1","article-title":"The genomic and clinical landscape of fetal akinesia","volume":"22","author":"Pergande","year":"2020","journal-title":"Genet. Med."},{"key":"ref_74","first-page":"617","article-title":"Novel ASCC1 mutations causing prenatal-onset muscle weakness with arthrogryposis and congenital bone fractures","volume":"56","author":"Malfatti","year":"2018","journal-title":"J. Med. Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"11939","DOI":"10.1093\/nar\/gky1093","article-title":"The neurodegenerative diseases ALS and SMA are linked at the molecular level via the ASC-1 complex","volume":"46","author":"Chi","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1002\/pd.5772","article-title":"Fetal MRI and ultrasound findings of a confirmed asparagine synthetase deficiency case","volume":"40","author":"Churchill","year":"2020","journal-title":"Prenat. Diagn."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"103624","DOI":"10.1016\/j.ejmg.2019.01.014","article-title":"Biallelic loss of function variants in ATP1A2 cause hydrops fetalis, microcephaly, arthrogryposis and extensive cortical malformations","volume":"63","author":"Monteiro","year":"2020","journal-title":"Eur. J. Med. Genet."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1002\/acn3.50882","article-title":"Dominant collagen XII mutations cause a distal myopathy","volume":"6","author":"Mohassel","year":"2019","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.jpeds.2016.12.060","article-title":"A Population-Based Study on Congenital Disorders of Protein N- and Combined with O-Glycosylation Experience in Clinical and Genetic Diagnosis","volume":"183","author":"Serrano","year":"2017","journal-title":"J. Pediatr."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.ymgme.2013.09.016","article-title":"Severe, fatal multisystem manifestations in a patient with dolichol kinase-congenital disorder of glycosylation","volume":"110","author":"Lieu","year":"2013","journal-title":"Mol. Genet. Metab."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41439-020-00116-8","article-title":"Arthrogryposis multiplex congenita with polymicrogyria and infantile encephalopathy caused by a novel GRIN1 variant","volume":"7","author":"Nishimura","year":"2020","journal-title":"Hum. Genome Var."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12881-017-0453-0","article-title":"A homozygous missense variant in HSD17B4 identified in a consanguineous Chinese Han family with type II Perrault syndrome","volume":"18","author":"Chen","year":"2017","journal-title":"BMC Med. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.jconrel.2014.03.021","article-title":"Muscle-targeted hydrodynamic gene introduction of insulin-like growth factor-1 using polyplex nanomicelle to treat peripheral nerve injury","volume":"183","author":"Nagata","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"103551","DOI":"10.1016\/j.ejmg.2018.10.003","article-title":"Two siblings with a novel nonsense variant provide further delineation of the spectrum of recessive KLHL7 diseases","volume":"62","author":"Jeffries","year":"2019","journal-title":"Eur. J. Med. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.ajhg.2020.06.014","article-title":"Mutations in MYLPF cause a novel segmental amyoplasia that manifests as distal arthrogryposis","volume":"107","author":"Chong","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Tan, L., Bi, B., Zhao, P., Cai, X., Wan, C., Shao, J., and He, X. (2017). Severe congenital microcephaly with 16p13.11 microdeletion combined with NDE1 mutation, a case report and literature review. BMC Med. Genet., 18.","DOI":"10.1186\/s12881-017-0501-9"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Bonnin, E., Cabochette, P., Filosa, A., J\u00fchlen, R., Komatsuzaki, S., Hezwani, M., Dickmanns, A., Martinelli, V., Vermeersch, M., and Supply, L. (2018). Biallelic mutations in nucleoporin NUP88 cause lethal fetal akinesia deformation sequence. PLoS Genet., 14.","DOI":"10.1371\/journal.pgen.1007845"},{"key":"ref_88","first-page":"E40","article-title":"Novel PLEC gene variants causing congenital myasthenic syndrome","volume":"60","author":"Garcia","year":"2019","journal-title":"Muscle Nerve"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2446","DOI":"10.1002\/ajmg.a.40479","article-title":"Phenotypic and molecular insights into PQBP1 -related intellectual disability","volume":"176","author":"Miyake","year":"2018","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/j.1365-2052.2006.01447.x","article-title":"Radiation hybrid mapping of 18 positional and physiological candidate genes for arthrogryposis multiplex congenita on porcine chromosome 5","volume":"37","author":"Genini","year":"2006","journal-title":"Anim. Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"S77","DOI":"10.1111\/epi.16319","article-title":"Phenotypic and genetic spectrum of SCN 8A -related disorders, treatment options, and outcomes","volume":"60","author":"Gardella","year":"2019","journal-title":"Epilepsia"},{"key":"ref_92","first-page":"513","article-title":"Recessive mutations in SCYL2 cause a novel syndromic form of arthrogryposis in humans","volume":"139","author":"Seidahmed","year":"2020","journal-title":"Qual. Life Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1002\/ajmg.a.61186","article-title":"SLC18A3 variants lead to fetal akinesia deformation sequence early in pregnancy","volume":"179","author":"Hakonen","year":"2019","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.ajhg.2019.08.006","article-title":"Loss of SMPD4 Causes a Developmental Disorder Characterized by Microcephaly and Congenital Arthrogryposis","volume":"105","author":"Magini","year":"2019","journal-title":"Am. J. Hum. Genet."},{"key":"ref_95","first-page":"106901","article-title":"Neurogenetic fetal akinesia and arthrogryposis: Genetics, expanding genotype-phenotypes and functional genomics","volume":"15","author":"Ravenscroft","year":"2020","journal-title":"J. Med. Genet."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e282","DOI":"10.1212\/NXG.0000000000000282","article-title":"Identification of a new SYT2 variant validates an unusual distal motor neuropathy phenotype","volume":"4","author":"Guan","year":"2018","journal-title":"Neurol. Genet."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/ng1511","article-title":"A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2","volume":"37","author":"Loeys","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1542\/peds.2016-1281","article-title":"Are Patients with Loeys-Dietz Syndrome Misdiagnosed with Beals Syndrome?","volume":"139","author":"Woolnough","year":"2017","journal-title":"Pediatrics"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/7\/1052\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:27:54Z","timestamp":1760164074000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/12\/7\/1052"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,8]]},"references-count":98,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["genes12071052"],"URL":"https:\/\/doi.org\/10.3390\/genes12071052","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,8]]}}}