title: Novel and recurrent mutations in the TAT gene in Tunisian families affected with Richner-Hanhart syndrome.
abstract: Tyrosinemia type II, also designated as oculocutaneous tyrosinemia or Richner-Hanhart syndrome (RHS), is a very rare autosomal recessive disorder. In the present study, we report clinical features and molecular genetic investigation of the tyrosine aminotransferase (TAT) gene in two young patients, both born to consanguineous unions between first-degree cousins. These two unrelated families originated from Northern and Southern Tunisia. The clinical diagnosis was based on the observation of several complications related to Richner-Hanhart syndrome: recurrent eye redness, tearing and burning pain, photophobia, bilateral pseudodendritic keratitis, an erythematous and painful focal palmo-plantar hyperkeratosis and a mild delay of mental development. The diagnosis was confirmed by biochemical analysis. Sequencing of the TAT gene revealed the presence of a previously reported missense mutation (c.452G>A, p.Cys151Tyr) in a Tunisian family, and a novel G duplication (c.869dupG, p.Trp291Leufs 6). Early diagnosis of RHS and protein-restricted diet are crucial to reduce the risk and the severity of long-term complications of hypertyrosinemia such as intellectual disability.
authors: Université Tunis El Manar, Institut Pasteur de Tunis, LR11IPT05, Génomique Biomédicale et Oncogénétique, 1002 Tunis,Tunisia; Université de Monastire, Institut Supérieur de Biotechnologie, Monastir 5000, Tunisia.
authors: Yosra
authors: Y
authors: Bouyacoub
authors: Hela
authors: H
authors: Zribi
authors: Hatem
authors: H
authors: Azzouz
authors: Fehmi
authors: F
authors: Nasrallah
authors: Rim Ben
authors: RB
authors: Abdelaziz
authors: Monia
authors: M
authors: Kacem
authors: Ben
authors: B
authors: Rekaya
authors: Olfa
authors: O
authors: Messaoud
authors: Lilia
authors: L
authors: Romdhane
authors: Cherine
authors: C
authors: Charfeddine
authors: Mustapha
authors: M
authors: Bouziri
authors: Sonia
authors: S
authors: Bouziri
authors: Neji
authors: N
authors: Tebib
authors: Mourad
authors: M
authors: Mokni
authors: Naziha
authors: N
authors: Kaabachi
authors: Samir
authors: S
authors: Boubaker
authors: Sonia
authors: S
authors: Abdelhak
mesh_terms: D000595:Amino Acid Sequence; D002675:Child, Preschool; D003241:Consanguinity; D018753:Diet, Protein-Restricted; D015756:Genes, tat; D006801:Humans; D007223:Infant; D007634:Keratitis / Q000150:complications / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D011487:Protein Conformation; D014416:Tunisia; D014444:Tyrosine Transaminase / Q000235:genetics / Q000378:metabolism; D020176:Tyrosinemias / Q000150:complications / Q000175:diagnosis / Q000235:genetics*
chemical_list: D014444:Tyrosine Transaminase
keywords: 3D; A; ABI; Adenine; Applied Biosystems; C; Cys; Cysteine; Cytosine; DNA; Degree Celsius; Deoxyribose Nucleic Acid; Duplication; Exo-SAP; Exonuclease-Shrimp Alcaline Phosphatase; Frameshift; G; Guanine; KCl; Kb; Kilobase; Leu; Leucine; Ligand-binding sites prediction; Lys; Lysine; MIM; Magnesium chloride; Mendelian Inheritance in Man; MgCl2; Microliter; Micromole per liter; Millimolar; Neonatal diagnosis; Novel mutation; PCR; Picomole; Polymerase Chain Reaction; Potassium Chloride; Pro; Proline; Protein; Richner–Hanhart syndrome; Second; T; Taq; Thermus aquaticus; Three-dimensional; Thymine; Tris(hydroxymethyl)aminomethane hydrochloride; Tris–HCl; Trp; Tryptophan; Tunisian families; Tyr; Tyrosine; dup; fs; mM; p; pmol; s; μL; μmol/L