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Cerebrofaciothoracic dysplasia: Four new patients with a recurrent TMCO1 pathogenic variant.
Am J Med Genet A. 2019 01; 179(1):43-49.AJ

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.

Authors+Show Affiliations

Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom.Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom.Academic Unit of Child Health, University of Sheffield, Sheffield, United Kingdom. Radiology Department, Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom.Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom.Dundee Clinical Genetics Service, Ninewells Hospital and Medical School, Dundee, United Kingdom.DDD Study, Wellcome Trust Sanger Institute, Cambridge, United Kingdom.Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30556256

Citation

Michael Yates, Thabo, et al. "Cerebrofaciothoracic Dysplasia: Four New Patients With a Recurrent TMCO1 Pathogenic Variant." American Journal of Medical Genetics. Part A, vol. 179, no. 1, 2019, pp. 43-49.
Michael Yates T, Ng OH, Offiah AC, et al. Cerebrofaciothoracic dysplasia: Four new patients with a recurrent TMCO1 pathogenic variant. Am J Med Genet A. 2019;179(1):43-49.
Michael Yates, T., Ng, O. H., Offiah, A. C., Willoughby, J., Berg, J. N., & Johnson, D. S. (2019). Cerebrofaciothoracic dysplasia: Four new patients with a recurrent TMCO1 pathogenic variant. American Journal of Medical Genetics. Part A, 179(1), 43-49. https://doi.org/10.1002/ajmg.a.60678
Michael Yates T, et al. Cerebrofaciothoracic Dysplasia: Four New Patients With a Recurrent TMCO1 Pathogenic Variant. Am J Med Genet A. 2019;179(1):43-49. PubMed PMID: 30556256.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cerebrofaciothoracic dysplasia: Four new patients with a recurrent TMCO1 pathogenic variant. AU - Michael Yates,Thabo, AU - Ng,Oon-Hui, AU - Offiah,Amaka C, AU - Willoughby,Josh, AU - Berg,Jonathan N, AU - ,, AU - Johnson,Diana S, Y1 - 2018/12/17/ PY - 2018/06/21/received PY - 2018/10/09/revised PY - 2018/10/14/accepted PY - 2018/12/18/pubmed PY - 2020/2/13/medline PY - 2018/12/18/entrez KW - TMCO1 KW - cerebrofaciothoracic dysplasia KW - intellectual disability SP - 43 EP - 49 JF - American journal of medical genetics. Part A JO - Am. J. Med. Genet. A VL - 179 IS - 1 N2 - 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. SN - 1552-4833 UR - https://www.unboundmedicine.com/medline/citation/30556256/Cerebrofaciothoracic_dysplasia:_Four_new_patients_with_a_recurrent_TMCO1_pathogenic_variant L2 - https://doi.org/10.1002/ajmg.a.60678 DB - PRIME DP - Unbound Medicine ER -