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TMCO1 deficiency causes autosomal recessive cerebrofaciothoracic dysplasia.
Am J Med Genet A 2014; 164A(2):291-304AJ

Abstract

Cerebrofaciothoracic dysplasia (CFT) (OMIM #213980) is a multiple congenital anomaly and intellectual disability syndrome involving the cranium, face, and thorax. The characteristic features are cranial involvement with macrocrania at birth, brachycephaly, various CT/MRI findings including hypoplasia of corpus callosum, enlargement of septum pellicidum, and diffuse hypodensity of the grey matter, flat face, hypertelorism, cleft lip and cleft palate, low-set, posteriorly rotated ears, short neck, and multiple costal and vertebral anomalies. The underlying genetic defect remains unknown. Using combination of homozygosity mapping and whole-exome sequencing, we identified a homozygous nonsense founder mutation, p.Arg87Ter (c.259 C>T), in the human transmembrane and coiled-coil domains protein 1 (TMCO1) in four out of five families of Turkish origin. The entire critical region on chromosome 1q24 containing TMCO1 was excluded in the fifth family with characteristic findings of CFT providing evidence for genetic heterogeneity of CFT spectrum. Another founder TMCO1 mutation has recently been reported to cause a unique genetic condition, TMCO1-defect syndrome (OMIM #614132). TMCO1-defect syndrome shares many features with CFT. This study supports the fact that "TMCO1-defect syndrome," initially thought to represent a distinct disorder, indeed belongs to the genetically heterogeneous CFT dysplasia spectrum.

Authors+Show Affiliations

Department of Pediatrics, Pediatric Genetics, Hacettepe University Medical Faculty, Ankara, Turkey; Department of Pediatrics, Pediatric Genetics, Acıbadem University Medical Faculty, Istanbul, Turkey.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

24194475

Citation

Alanay, Yasemin, et al. "TMCO1 Deficiency Causes Autosomal Recessive Cerebrofaciothoracic Dysplasia." American Journal of Medical Genetics. Part A, vol. 164A, no. 2, 2014, pp. 291-304.
Alanay Y, Ergüner B, Utine E, et al. TMCO1 deficiency causes autosomal recessive cerebrofaciothoracic dysplasia. Am J Med Genet A. 2014;164A(2):291-304.
Alanay, Y., Ergüner, B., Utine, E., Haçariz, O., Kiper, P. O., Taşkıran, E. Z., ... Akarsu, N. A. (2014). TMCO1 deficiency causes autosomal recessive cerebrofaciothoracic dysplasia. American Journal of Medical Genetics. Part A, 164A(2), pp. 291-304. doi:10.1002/ajmg.a.36248.
Alanay Y, et al. TMCO1 Deficiency Causes Autosomal Recessive Cerebrofaciothoracic Dysplasia. Am J Med Genet A. 2014;164A(2):291-304. PubMed PMID: 24194475.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TMCO1 deficiency causes autosomal recessive cerebrofaciothoracic dysplasia. AU - Alanay,Yasemin, AU - Ergüner,Bekir, AU - Utine,Eda, AU - Haçariz,Orçun, AU - Kiper,Pelin Ozlem Simsek, AU - Taşkıran,Ekim Zihni, AU - Perçin,Ferda, AU - Uz,Elif, AU - Sağiroğlu,Mahmut Şamil, AU - Yuksel,Bayram, AU - Boduroglu,Koray, AU - Akarsu,Nurten Ayse, Y1 - 2013/11/05/ PY - 2013/06/19/received PY - 2013/08/19/accepted PY - 2013/11/7/entrez PY - 2013/11/7/pubmed PY - 2014/9/12/medline KW - TMCO1 KW - TMCO1-defect KW - cerebrofaciothoracic dysplasia KW - whole exome-sequencing SP - 291 EP - 304 JF - American journal of medical genetics. Part A JO - Am. J. Med. Genet. A VL - 164A IS - 2 N2 - Cerebrofaciothoracic dysplasia (CFT) (OMIM #213980) is a multiple congenital anomaly and intellectual disability syndrome involving the cranium, face, and thorax. The characteristic features are cranial involvement with macrocrania at birth, brachycephaly, various CT/MRI findings including hypoplasia of corpus callosum, enlargement of septum pellicidum, and diffuse hypodensity of the grey matter, flat face, hypertelorism, cleft lip and cleft palate, low-set, posteriorly rotated ears, short neck, and multiple costal and vertebral anomalies. The underlying genetic defect remains unknown. Using combination of homozygosity mapping and whole-exome sequencing, we identified a homozygous nonsense founder mutation, p.Arg87Ter (c.259 C>T), in the human transmembrane and coiled-coil domains protein 1 (TMCO1) in four out of five families of Turkish origin. The entire critical region on chromosome 1q24 containing TMCO1 was excluded in the fifth family with characteristic findings of CFT providing evidence for genetic heterogeneity of CFT spectrum. Another founder TMCO1 mutation has recently been reported to cause a unique genetic condition, TMCO1-defect syndrome (OMIM #614132). TMCO1-defect syndrome shares many features with CFT. This study supports the fact that "TMCO1-defect syndrome," initially thought to represent a distinct disorder, indeed belongs to the genetically heterogeneous CFT dysplasia spectrum. SN - 1552-4833 UR - https://www.unboundmedicine.com/medline/citation/24194475/TMCO1_deficiency_causes_autosomal_recessive_cerebrofaciothoracic_dysplasia_ L2 - https://doi.org/10.1002/ajmg.a.36248 DB - PRIME DP - Unbound Medicine ER -