title: The P28T mutation in the GALK1 gene accounts for galactokinase deficiency in Roma (Gypsy) patients across Europe.
abstract: 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.
authors.affiliation: Centre for Human Genetics, Edith Cowan University, Perth, W.A., Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Hunter
authors.forename: Evelyne
authors.initials: E
authors.lastname: Heyer
authors.forename: Frederic
authors.initials: F
authors.lastname: Austerlitz
authors.forename: Dora
authors.initials: D
authors.lastname: Angelicheva
authors.forename: Vania
authors.initials: V
authors.lastname: Nedkova
authors.forename: Paz
authors.initials: P
authors.lastname: Briones
authors.forename: Anna
authors.initials: A
authors.lastname: Gata
authors.forename: Rosaario
authors.initials: R
authors.lastname: de Pablo
authors.forename: Aranka
authors.initials: A
authors.lastname: László
authors.forename: Nills
authors.initials: N
authors.lastname: Bosshard
authors.forename: Richard
authors.initials: R
authors.lastname: Gitzelmann
authors.forename: Attila
authors.initials: A
authors.lastname: Tordai
authors.forename: Lajos
authors.initials: L
authors.lastname: Kalmar
authors.forename: Csaba
authors.initials: C
authors.lastname: Szalai
authors.forename: Istvan
authors.initials: I
authors.lastname: Balogh
authors.forename: Contantin
authors.initials: C
authors.lastname: Lupu
authors.forename: Axinia
authors.initials: A
authors.lastname: Corches
authors.forename: Gabriela
authors.initials: G
authors.lastname: Popa
authors.forename: Anna
authors.initials: A
authors.lastname: Perez-Lezaun
authors.forename: Luba Vd
authors.initials: LV
authors.lastname: Kalaydjieva
mesh_terms: 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
chemical_list: D005686:Galactokinase