Yates, T.M., Ng, O.-H., Offiah, A.C. orcid.org/0000-0001-8991-5036 et al. (4 more authors) (2019) Cerebrofaciothoracic dysplasia: four new patients with a recurrent TMCO1 pathogenic variant. American Journal of Medical Genetics Part A, 179 (1). pp. 43-49. ISSN 1552-4825
Abstract
Biallelic loss of function variants in the TMCO1 gene have been previously demonstrated to result in cerebrofaciothoracic dysplasia (CFTD; MIM #213980). The phenotype of this condition includes severe intellectual disability, as well as distinctive craniofacial features, including brachycephaly, synophrys, arched eyebrows, "cupid's bow" upper lip, and microdontia. In addition, nonspecific skeletal anomalies are common, including bifid ribs, scoliosis, and spinal fusion. Only 19 molecularly confirmed patients have been previously described. Here, we present four patients with CFTD, including three brothers from a Pakistani background and an additional unrelated white Scottish patient. All share the characteristic craniofacial appearance, with severe intellectual disability and skeletal abnormalities. We further define the phenotype with comparison to the published literature, and present images to define the dysmorphic features in a previously unreported ethnic group. All of our patient series are homozygous for the same c.292_293del (p.Ser98*) TMCO1 pathogenic variant, which has been previously reported only in an isolated Amish population. Thus we provide evidence that CFTD may be more common than previously thought. The patients presented here further delineate the phenotypic spectrum of CFTD and provide evidence for a recurrent pathogenic variant in TMCO1.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018, Wiley. This is an author produced version of a paper subsequently published in the American Journal of Medical Genetics Part A. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Cerebrofaciothoracic dysplasia; Intellectual disability; TMCO1 |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 07 Jan 2019 13:21 |
Last Modified: | 25 Nov 2021 08:28 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/ajmg.a.60678 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:140464 |