Genetic basis of cystinosis in Tunisian patients: Identification of novel mutation in CTNS gene.
Nephropathic cystinosis (NC) is an autosomal recessive disorder characterized by defective transport of cystine across the lysosomal membrane and resulting in renal, ophthalmic, and other organ abnormalities. Mutations in the CTNS gene cause a deficiency of the transport protein, cystinosin. This study was performed to investigate mutations of the CTNS gene in three Tunisian families with NC. Polymerase chain reaction (PCR), ARMS multiplex PCR and direct sequencing were performed for molecular characterization of the CTNS gene in 3 unrelated Tunisian patients and their parents. Based on family history, prenatal diagnosis (PND) was performed in fetal DNA isolated from chorionic villi obtained at 10-12  weeks of gestation. None of the patients showed the most common 57-kb deletion in heterozygous or homozygous status. One patient was homozygous for the previously reported mutation c.1515G > A (p.G308R). One patient presented the novel gross deletion of 20,327 bp. One was homozygote for the previously reported mutation c.771_793del (p.Gly258Serfs*30). In addition, eight polymorphisms were identified in the 3 patients and their parents. The prenatal diagnosis in one family showed that the fetus DNA was heterozygous for the c.771_793del (p.Gly258Serfs*30) mutation. This study expands the mutational and population spectrum of NC, representing the first molecular diagnosis of NC in Tunisian population. The mutation screening of the CTNS gene was used for prenatal diagnosis to prevent and/or limit this inheritable disease in our country where the families are particularly large and have a high rate of consanguinity.
Laboratory of Biochemistry, F. Hached Hospital, 4000 Sousse, Tunisia ; University of Monastir, 5000 Monastir, Tunisia.
Latifa
L
Chkioua
Laboratory of Biochemistry, F. Hached Hospital, 4000 Sousse, Tunisia ; University of Monastir, 5000 Monastir, Tunisia.
Souhir
S
Khedhiri
Laboratory of Biochemistry, F. Hached Hospital, 4000 Sousse, Tunisia.
Oussama
O
Grissa
The Auvergne-Loire Regional Branch of the French National Blood System EFS/GIMAP-EA 3064, 42100 Saint Etienne, France.
Chaker
C
Aloui
Laboratory of Pediatrics, La Rabta Hospital, 1007 Tunis, Tunisia.
Hadhami Ben
HB
Turkia
Laboratory of Biochemistry, F. Hached Hospital, 4000 Sousse, Tunisia ; University of Monastir, 5000 Monastir, Tunisia.
Salima
S
Ferchichi
Laboratory of Biochemistry, F. Hached Hospital, 4000 Sousse, Tunisia ; University of Monastir, 5000 Monastir, Tunisia.
Abdelhedi
A
Miled
Hereditary Metabolic Diseases Service, East Center for Biology and Pathology, Lyon Civil Hospices 69677 Bron cedex, France.
Roseline
R
Froissart
Hereditary Metabolic Diseases Service, East Center for Biology and Pathology, Lyon Civil Hospices 69677 Bron cedex, France.
Cecile
C
Acquaviva
The Auvergne-Loire Regional Branch of the French National Blood System EFS/GIMAP-EA 3064, 42100 Saint Etienne, France.
Sandrine
S
Laradi
CTNS; Mutations; Nephropathic cystinosis; Polymorphisms; Prenatal diagnosis; Tunisian families