Samilchuk et al. (2001) studied the UGT1A1 gene promoter polymorphism among 55 unrelated Kuwaiti blood donors with G6PD deficiency cased by the Mediterranean mutation, by using PCR followed by polyacrylamide gel electrophoresis (PAGE). Among the 55 studied subjects, nine individuals were found to be homozygous and 26 heterozygous for the (TA)7. The frequencies of the (TA)6 and (TA)7 alleles were 0.6 and 0.4, respectively. Samilchuk et al. (2001) concluded that high frequency of the (TA)7 allele and Mediterranean mutation among Kuwaitis may produce neonatal jaundice in up to 1% of the male and 0.6% of the female newborns.

[Samilchuk E, Al-Suleiman I, Usanga E, Al-Awadi S. UDP Glucuronosyltransferase 1 (UGT1A1) Gene Promoter Polymorphism among Kuwaitis with Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency. Kuwait Med J. 2001, 33 (1):22-25]

Koshy et al. (2004) conducted DNA analysis in affected members of Kuwaiti Bedouin families with Crigler-Najjar syndrome. The patients were found to carry an A-to-G transition converting codon 357 from CAA (gln) to CGA (arg) (Q357R). Furthermore, the patients also carried a TA insertion within the promoter of the UGT1A1 gene.

[See also: Tunisia > Petit et al., 2008].

Labrune et al. (1994) reported two patients from Tunisia with Crigler-Najjar syndrome type I. By DNA analysis they found the mutation Q357R in the two patients. In 2002, Francoual et al. (2002a) studied six patients with Crigler-Najjar syndrome type I who originated from different parts of Tunisia and were not related to each other. In each patient the diagnosis of the disorder was clinically and biochemically suspected, then confirmed by enzymatic assay. The patients were found to carry an A-to-G transition converting codon 357 from CAA (gln) to CGA (arg) (Q357R). Furthermore, the six patients were homozygous for a TA insertion within the promoter of the UGT1A1 gene, thus resulting in TA7/TA7 homozygosity. All 12 parents were heterozygous for the Q357R mutation and the TA7 allele. These resulted indicated that Crigler-Najjar syndrome type I in Tunisia may be associated with a founder effect related to the Q357R mutation within the UGT1 gene. In the same year, Francoual et al. (2002b) reported DNA-based prenatal diagnosis of CN-I in two Tunisian families in whom CN-I patients were diagnosed; thus avoiding the need for enzymatic assay on liver tissue, which requires performing a liver needle biopsy. In both cases, SSCP analysis of fetal DNA showed that the fetus was heterozygous for the Q357R mutation. In both families, the pregnancies were continued.

In order to determine the origin of the c.1070A4G mutation in the UGT1A1 gene, Petit et al. (2008) investigated 21 Tunisian and 2 Kuwaiti Crigler-Najjar type 1 syndrome (CN-1) patients and 28 healthy unrelated Tunisian controls for genetic markers on both centromeric and telomeric sides of c.1070A-G mutation in UGT1A1 gene. The investigation revealed the possibility that this mutation emerged in Bedouin nomad groups and then spread in Tunisia approximately eight centuries ago after the migration of populations from the Middle East to Maghreb. Additionally, clinical and/or biochemical CN-I was genetically confirmed for 56 patients. Twenty-five of these patients originated from different part of Tunisia (Tunis, Sfax and Sousse) and 21 were found to be homozygous for the c.1070A4G mutation in exon 3 associated with the A(TA)7TAA/A(TA)7TAA polymorphism in the TATA box (three of the other patients were found to be homozygous for the deletion c.396_401delCAACAA associated with the A(TA)7TAA/A(TA)7TAA polymorphism and the fourth was found to be homozygous for a large deletion including the promoter and the exon 1. In the Tunisian population, the Gilbert allele A(TA)7TAA frequency was found to be 0.393 and 0.178 for heterozygotes and homozygotes, respectively, comparable to those observed in France and Greece.