A high degree of molecular heterogeneneity at the phenylalanine hydroxylase
(PAH) locus was established by examining RFLP haplotypes and PAH mutations
in the families of 13 Egyptians with phenylketenouria (PKU), Thirteen diff
erent haplotypes were unequivocally determined in these kindreds, Haplotype
s 1.8, 3.9, 4.3, 7.8, 22.11, 27.6, and 52.8 were found segregating with nor
mal chromosomes, whilst haplotypes 1.8, 5.9, 23.8, 32.8, the newly assigned
73.9, and two as yet incomplete but novel haplotypes were found segregatin
g with the mutant chromosomes, There was no particular preference for a sin
gle haplotype among normal or mutant chromosomes. Nine different mutations
were also identified among the 26 alleles. IVS 10nt11g (8/26), IVS 2nt5g-c
(4/26), R261Q (3/26), R176X (2/26), Y206D (2/26), S231P (2/26) Y198fs [593-
614del22bp]; (2/26), G46fs [136/137delG]; (1/26), and E178G (Y26), Six of t
hese mutations (IVS 2nt5g-c, R176X, Y198fs, R261Q, S231P, and IVS 10nt11g)
are common to other Mediterranean populations, Two mutations not previously
reported in the Mediterranean basin were also observed (Y206D and G46fs),
These intriguing preliminary findings confirm IVS 10nt11g as a major mutati
on among Mediterranean mutations and demonstrate the need for a more compre
hensive study of Arab populations to confirm the uniqueness of the two nove
l mutations to the Egyptian population.