The P28T mutation in the GALK1 gene accounts for galactokinase deficiency in Roma (Gypsy) patients across Europe.
Galactokinase deficiency is an inborn error of metabolism that, if untreated, results in the development of cataracts in the first weeks of life. The disorder is rare worldwide, but has a high incidence among the Roma (Gypsies). In 1999, we reported the founder Romani mutation, P28T, identified in affected families from Bulgaria. Subsequent studies have detected the same mutation in Romani patients from different European countries. The screening of 803 unrelated control individuals of Romani ethnicity from Bulgaria, Hungary, and Spain has shown an overall carrier rate of 1:47 and an expected incidence of affected births about 1:10,000. Using disease haplotype analysis, the age of the P28T mutation was estimated at 750 y, preceding the splits of the proto-Roma into the numerous populations resident in Europe today. The findings suggest that the mutation has spread with the early diaspora of the Roma throughout Europe. Superimposed on this old distribution pattern is the new migration wave of the last decade, with large numbers of Roma moving to Western Europe as a result of the economic changes in the East and the wars in former Yugoslavia. The changing demographic pattern of Romani minorities can be expected to lead to a homogenization of the incidence of "private" Romani disorders and founder mutations. The P28T mutation is thus likely to account for a high proportion of galactokinase deficiency cases across Europe. Mutation-based pilot newborn screening programs would provide current incidence figures and help to design long-term prevention of infantile cataracts due to galactokinase deficiency.
Hunter
Michael
M
Centre for Human Genetics, Edith Cowan University, Perth, W.A., Australia.
Heyer
Evelyne
E
Austerlitz
Frederic
F
Angelicheva
Dora
D
Nedkova
Vania
V
Briones
Paz
P
Gata
Anna
A
de Pablo
Rosaario
R
László
Aranka
A
Bosshard
Nills
N
Gitzelmann
Richard
R
Tordai
Attila
A
Kalmar
Lajos
L
Szalai
Csaba
C
Balogh
Istvan
I
Lupu
Contantin
C
Corches
Axinia
A
Popa
Gabriela
G
Perez-Lezaun
Anna
A
Kalaydjieva
Luba Vd
LV
D019943:Amino Acid Substitution; D002031:Bulgaria / Q000208:ethnology; D003241:Consanguinity; D005060:Europe / Q000453:epidemiology; D018703:Founder Effect; D005686:Galactokinase / Q000235:genetics*; D005693:Galactosemias / Q000208:ethnology* / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D020125:Mutation, Missense; D010375:Pedigree; D017354:Point Mutation; D006178:Romani People / Q000235:genetics*; D013030:Spain / Q000453:epidemiology; D013557:Switzerland / Q000453:epidemiology; D014421:Turkey / Q000208:ethnology
D005686:Galactokinase