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Novel copy number variants and major limb reduction malformation: Report of three cases
Author(s) -
Shamseldin Hanan E.,
Anazi Shams,
Wakil Salma M.,
Faqeih Eissa,
El Khashab Heba Y.,
Salih Mustafa A.,
AlQattan Mohammad M.,
Hashem Mais,
Alsedairy Haifa,
Alkuraya Fowzan S.
Publication year - 2016
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37550
Subject(s) - copy number variation , limb development , biology , karyotype , genetics , gene , medicine , bioinformatics , chromosome , genome
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. © 2016 Wiley Periodicals, Inc.