Clinical and mutational investigations of tyrosinemia type II in Northern Tunisia: identification and structural characterization of two novel TAT mutations
| Autor: | A. Laadjimi, Cherine Charfeddine, Sonia Abdelhak, Neji Tebib, M.F. Ben Dridi, M. Keirallah, M. N. Guediche, M. Nilges, Kamel Monastiri, Mohamed Ridha Kamoun, Samir Boubaker, A. Ben Osman, Selma Kassar, Mourad Mokni, Naziha Kaabachi, O. Perin |
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| Přispěvatelé: | Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP), CHU Fattouma Bourguiba [Monastir] (HFB), Hôpital La Rabta [Tunis], Bioinformatique structurale - Structural Bioinformatics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles Nicolle [Tunis], This work was supported by the Tunisian Ministry of Scientific and Technological Research and, Development of Competencies (Research Unit on 'Molecular Investigation of Genetic Orphan Diseases' UR 26/04 and Research Unit on 'Study of Hereditary Keratinization Disorders' UR 24/04)., We thank the patients and family members., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
Male
Models Molecular Clinical heterogeneity Endocrinology Diabetes and Metabolism Mutant medicine.disease_cause Biochemistry Consanguinity 030207 dermatology & venereal diseases Exon 0302 clinical medicine Endocrinology Tyrosine aminotransferase Pregnancy Structural models Haplotype analysis Missense mutation Child Tyrosinemia type II Genetics 0303 health sciences Mutation Tyrosinemias Phenotype Pedigree 3. Good health Child Preschool Female Amino acidemias Adult Tunisia Molecular Sequence Data Mutation Missense Biology Mutation screening 03 medical and health sciences medicine Humans Amino Acid Sequence Molecular Biology Tyrosine Transaminase 030304 developmental biology medicine.disease Molecular biology Haplotypes Tyrosine [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology Microsatellite Repeats |
| Zdroj: | Molecular Genetics and Metabolism Molecular Genetics and Metabolism, Elsevier, 2006, 88 (2), pp.184--91. ⟨10.1016/j.ymgme.2006.02.006⟩ Molecular Genetics and Metabolism, 2006, 88 (2), pp.184--91. ⟨10.1016/j.ymgme.2006.02.006⟩ |
| ISSN: | 1096-7192 1096-7206 |
| DOI: | 10.1016/j.ymgme.2006.02.006⟩ |
| Popis: | International audience; Tyrosinemia type II or Richner-Hanhart Syndrome (RHS) is an autosomal recessive disorder characterized by keratitis, palmoplantar keratosis, mental retardation, and elevated blood tyrosine levels. The disease is due to a deficiency of hepatic cytosolic tyrosine aminotransferase (TATc), an enzyme involved in the tyrosine catabolic pathway. Because of the high rate of consanguinity this disorder seems to be relatively common among the Arab and Mediterranean populations. RHS is characterized by inter and intrafamilial phenotypic variability. A large spectrum of mutations within TATc gene has been shown to be responsible for RHS. In the present study, we report the clinical features and the molecular investigation of RHS in three unrelated consanguineous Tunisian families including 7 patients with confirmed biochemical diagnosis of tyrosinemia type II. Mutation analyses were performed and two novel missense mutations were identified (C151Y) and (L273P) within exon 5 and exon 8, respectively. The 3D-structural characterization of these mutations provides evidence of defective folding of the mutant proteins, and likely alteration of the enzymatic activity. Phenotype variability was observed even among individuals sharing the same pathogenic mutation. |
| Databáze: | OpenAIRE |
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