A novel biallelic loss-of-function mutation in TMCO1 gene confirming and expanding the phenotype spectrum of cerebro-facio-thoracic dysplasia
Autor: | Abdussalam Azem, Holger Hengel, Ludger Schöls, Rajech Sharkia, Abdelnaser Zalan, Azhar Jabareen-Masri, Muhammad Mahajnah, Amit Kessel |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Male Pediatrics medicine.medical_specialty Disease 030105 genetics & heredity Gene mutation genetics [Craniofacial Abnormalities] Craniofacial Abnormalities 03 medical and health sciences Epilepsy Exon abnormalities [Brain] pathology [Craniofacial Abnormalities] Loss of Function Mutation Intellectual disability Genetics medicine Humans pathology [Thorax] ddc:610 Genetics (clinical) Alleles business.industry Brain Thorax medicine.disease Cerebro-facio-thoracic dysplasia Pedigree 030104 developmental biology Phenotype Dysplasia genetics [Calcium Channels] Mutation (genetic algorithm) Mutation Female Calcium Channels business |
Zdroj: | American journal of medical genetics / A 179(7), ajmg.a.61168 (2019). doi:10.1002/ajmg.a.61168 |
Popis: | 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. |
Databáze: | OpenAIRE |
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