Molecular and clinical evaluation of primary congenital glaucoma in Kuwait.
OBJECTIVE
To report the spectrum of the CYP1B1 mutation in Kuwaiti patients with primary congenital glaucoma (PCG).


METHODS
Clinical diagnosis of PCG and laboratory based experimental study.


METHODS
Polymerase chain reaction-restriction polymorphism length fragment (PCR-RPLF) and direct sequencing of exon 2 and the coding region of exon 3 of CYP1B1 gene were the methods used for screening 17 PCG patients, their families, and 105 health individuals from the same ethnicity.


RESULTS
Four different mutations were detected in CYP1B1 in 70.6% of the screened patients. The most common one (47%) was homozygote Gly61Glu mutation, previously described in Saudi Arabia, Turkey, and Morocco; all patients were products of consanguineous marriages. The second common mutation was a novel missense (Ala388Thr) mutation found in three patients (17.6%) as compound heterozygote with Arg368His in one patient, and with Gly61Glu in another one while the second mutation in third patient was not detected in the CYP1B1 gene. One patient (5.8%) was homozygote for Cyt280X mutation previously reported in only one Japanese family. In addition to these mutations, a novel Val422Gly polymorphic site was found in three of the PCG patients and in 18 of the 210 tested chromosomes of healthy volunteers.


CONCLUSIONS
The CYP1B1 mutation spectrum of Kuwaiti PCG patients is similar to that detected in the neighboring countries. No clear genotype-phenotype correlation detected in patients showed different types of CYP1B1 mutation.
Alfadhli
Suad
S
Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Kuwait University, PO Box 31470 Sulaibekhat, Kuwait. s.alfadhli@hsc.edu.kw
Behbehani
Abdulmutalib
A
Elshafey
Alaa
A
Abdelmoaty
Sidky
S
Al-Awadi
Sadiqa
S
D001189:Aryl Hydrocarbon Hydroxylases; D002675:Child, Preschool; D003241:Consanguinity; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005820:Genetic Testing; D005901:Glaucoma / Q000151:congenital* / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007429:Intraocular Pressure; D007730:Kuwait / Q000453:epidemiology; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA
D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1