TY - JOUR
T1 - A novel biallelic loss-of-function mutation in TMCO1 gene confirming and expanding the phenotype spectrum of cerebro-facio-thoracic dysplasia
AU - Sharkia, Rajech
AU - Zalan, Abdelnaser
AU - Jabareen-Masri, Azhar
AU - Hengel, Holger
AU - Schöls, Ludger
AU - Kessel, Amit
AU - Azem, Abdussalam
AU - Mahajnah, Muhammad
N1 - Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
PY - 2019/7
Y1 - 2019/7
N2 - The main clinical features of cerebro-facio-thoracic dysplasia (CFTD) syndrome, which were described over four decades ago, include facial dysmorphism, multiple malformations of the vertebrae and ribs, and intellectual disability. Recently, a TMCO1 gene mutation was shown to be responsible for an autosomal recessive CFTD syndrome characterized by craniofacial dysmorphism, skeletal anomalies, and intellectual disability. In the current report, we describe two members of a consanguineous family from an Arab community in Israel who were clinically diagnosed as suffering from craniofacial dysmorphism, skeletal anomalies, intellectual disability, and epilepsy. Both affected siblings had behavioral difficulties such as anxiety and emotional instability with impulsive behaviors. Whole-exome sequencing revealed a homozygous stop-gain mutation NM_019026.4: c.616C > T; p.(Arg206*) in exon 6 of the TMCO1 gene. Bioinformatics analysis suggested a structural model for the TMCO1 protein and its homologues. The clinical features of our patients were compared with those of the only other five studies available in the literature. We conclude that this mutation in the TMCO1 gene is responsible for the various clinical manifestations of CFTD syndrome exhibited by the patients studied that expand the phenotypic spectrum of the disease to include epilepsy as a characteristic feature of this syndrome.
AB - The main clinical features of cerebro-facio-thoracic dysplasia (CFTD) syndrome, which were described over four decades ago, include facial dysmorphism, multiple malformations of the vertebrae and ribs, and intellectual disability. Recently, a TMCO1 gene mutation was shown to be responsible for an autosomal recessive CFTD syndrome characterized by craniofacial dysmorphism, skeletal anomalies, and intellectual disability. In the current report, we describe two members of a consanguineous family from an Arab community in Israel who were clinically diagnosed as suffering from craniofacial dysmorphism, skeletal anomalies, intellectual disability, and epilepsy. Both affected siblings had behavioral difficulties such as anxiety and emotional instability with impulsive behaviors. Whole-exome sequencing revealed a homozygous stop-gain mutation NM_019026.4: c.616C > T; p.(Arg206*) in exon 6 of the TMCO1 gene. Bioinformatics analysis suggested a structural model for the TMCO1 protein and its homologues. The clinical features of our patients were compared with those of the only other five studies available in the literature. We conclude that this mutation in the TMCO1 gene is responsible for the various clinical manifestations of CFTD syndrome exhibited by the patients studied that expand the phenotypic spectrum of the disease to include epilepsy as a characteristic feature of this syndrome.
KW - Arabs in Israel
KW - TMCO1 mutation
KW - cerebro-facio-thoracic dysplasia
KW - epilepsy
UR - http://www.scopus.com/inward/record.url?scp=85066013318&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.61168
DO - 10.1002/ajmg.a.61168
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C2 - 31102500
AN - SCOPUS:85066013318
SN - 1552-4825
VL - 179
SP - 1338
EP - 1345
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 7
ER -