Novel and recurrent mutations in the TAT gene in Tunisian families affected with Richner-Hanhart Syndrome.

Yosra Bouyacoub (1, 2) , Hela Zribi (3) , Hatem Azzouz (4) , Fehmi Nasrallah (5) , Rim Ben Abdelaziz (4) , Monia Kacem (2) , Ben Rekaya (2) , Olfa Messaoud (2) , Lilia Romdhane (2) , Cherine Charfeddine (2) , Mustapha Bouziri (6) , Sonia Bouziri (7) , Neji Tebib (4) , Mourad Mokni (3) , Naziha Kaabachi (5) , Samir Boubaker (2) , Sonia Abdelhak (2)

1 ISBM - Institut Supérieur de Biotechnologie de Monastir
2 LR11IPT05 - Laboratoire de Génomique Biomédicale et Oncogénétique - Biomedical Genomics and Oncogenetics Laboratory
3 Département de Dermatologie, U.R. Etude des maladies héréditaires de Kératinisation
4 Département de Pédiatrie, Unité des maladies métaboliques héréditaires
5 Laboratoire de Biochimie
6 Private practice
7 Départment de Pédiatrie

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.

Mots clés: Richner-Hanhart syndrome; Novel mutation; Tunisian families Ligand-binding sites prediction; Neonatal diagnosis

Domaines: Sciences du Vivant [q-bio]

Yosra Bouyacoub, Hela Zribi, Hatem Azzouz, Fehmi Nasrallah, Rim Ben Abdelaziz, et al.. Novel and recurrent mutations in the TAT gene in Tunisian families affected with Richner-Hanhart Syndrome.. Gene, 2013, 529 (1), pp.45-9. ⟨10.1016/j.gene.2013.07.066⟩. ⟨pasteur-00861205⟩