Novel copy number variants and major limb reduction malformation: Report of three cases.
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.
['Shamseldin|Hanan E|HE|', 'Anazi|Shams|S|', 'Wakil|Salma M|SM|', 'Faqeih|Eissa|E|', 'El Khashab|Heba Y|HY|', 'Salih|Mustafa A|MA|', 'Al-Qattan|Mohammad M|MM|', 'Hashem|Mais|M|', 'Alsedairy|Haifa|H|', 'Alkuraya|Fowzan S|FS|']
D002675:Child, Preschool D056915:DNA Copy Number Variations D004476:Ectodermal Dysplasia D006801:Humans D007223:Infant D017880:Limb Deformities, Congenital D008297:Male D008565:Membrane Proteins D009154:Mutation D012529:Saudi Arabia D012536:Scalp Dermatoses D020825:T-Box Domain Proteins D020830:rac1 GTP-Binding Protein
RAC1 TBX3 TBX5 LMBR1 Adams-Oliver syndrome CGH