title: Novel copy number variants and major limb reduction malformation: Report of three cases.
abstract: Limb reduction malformations are highly heterogeneous in their clinical presentation and so, predicting the underlying mutation on a clinical basis can be challenging. Molecular karyotyping is a powerful genomic tool that has quickly become the mainstay for the study of children with malformation syndromes. We describe three patients with major limb reduction anomalies in whom pathogenic copy number variants were identified on molecular karyotyping. These include a patient with hypoplastic phalanges and absent hallux bilaterally with de novo deletion of 11.9 Mb on 7p21.1-22.1 spanning 63 genes including RAC1, another patient with severe Holt-Oram syndrome and a large de novo deletion 2.2 Mb on 12q24.13-24.21 spanning 20 genes including TBX3 and TBX5, and a third patient with acheiropodia who had a nullizygous deletion of 102 kb on 7q36.3 spanning LMBR1. We discuss the potential of these novel genomic rearrangements to improve our understanding of limb development in humans.
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Hanan E
authors.initials: HE
authors.lastname: Shamseldin
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Shams
authors.initials: S
authors.lastname: Anazi
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Salma M
authors.initials: SM
authors.lastname: Wakil
authors.affiliation: Department of Pediatric Specialties, Children's Hospital, King Fahad Medical City, Riyadh, Saudi Arabia.
authors.forename: Eissa
authors.initials: E
authors.lastname: Faqeih
authors.affiliation: Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.|Department of Pediatrics, Children's Hospital, Ain Shams University, Cairo, Egypt.
authors.forename: Heba Y
authors.initials: HY
authors.lastname: El Khashab
authors.affiliation: Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mustafa A
authors.initials: MA
authors.lastname: Salih
authors.affiliation: Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mohammad M
authors.initials: MM
authors.lastname: Al-Qattan
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Mais
authors.initials: M
authors.lastname: Hashem
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Haifa
authors.initials: H
authors.lastname: Alsedairy
authors.affiliation: Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.|Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D002675:Child, Preschool; D056915:DNA Copy Number Variations / Q000235:genetics; D004476:Ectodermal Dysplasia / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007223:Infant; D017880:Limb Deformities, Congenital / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D012529:Saudi Arabia; D012536:Scalp Dermatoses / Q000151:congenital* / Q000235:genetics / Q000503:physiopathology; D020825:T-Box Domain Proteins / Q000235:genetics*; D020830:rac1 GTP-Binding Protein / Q000235:genetics*
chemical_list: C485955:LMBR1 protein, human; D008565:Membrane Proteins; C107953:RAC1 protein, human; D020825:T-Box Domain Proteins; C103172:T-box transcription factor 5; C106884:TBX3 protein, human; D020830:rac1 GTP-Binding Protein
keywords: Adams-Oliver syndrome; CGH; LMBR1; RAC1; TBX3; TBX5