title: Genetic basis of transferase-deficient galactosaemia in Ireland and the population history of the Irish Travellers.
abstract: Transferase-deficient galactosaemia, resulting from deficient activity of galactose-1-phosphate uridyltransferase (GALT), is relatively common among the Travellers, an endogamous group of commercial/industrial nomads within the Irish population. This study has estimated the incidence of classical transferase-deficient galactosaemia in Ireland and determined the underlying GALT mutation spectrum in the Irish population and in the Traveller group. Based upon a survey of newborn screening records, the incidence of classical transferase-deficient galactosaemia was estimated to be 1 in 480 and 1 in 30,000 among the Traveller and non-Traveller communities respectively. Fifty-six classical galactosaemic patients were screened for mutation in the GALT locus by standard molecular methods. Q188R was the sole mutant allele among the Travellers and the majority mutant allele among the non-Travellers (89.1%). Of the five non-Q188R mutant alleles in the non-Traveller group, one was R333G and one F194L with three remaining uncharacterized. Anonymous population screening has shown the Q188R carrier frequency to be 0.092 or 1 in 11 among the Travellers as compared with 0.009 or 1 in 107 among the non-Travellers. The Q188R mutation was shown to be in linkage disequilibrium with a Sac I RFLP flanking exon 6 of the GALT gene. This represents the first molecular genetic description of classical transferase-deficient galactosaemia in Ireland and raises intriguing questions concerning the genetic history of the Irish Travellers.
authors.affiliation: Department of Pathology, Children's Hospital, Royal College of Surgeons in Ireland, Dublin, Republic of Ireland.
authors.forename: M
authors.initials: M
authors.lastname: Murphy
authors.forename: B
authors.initials: B
authors.lastname: McHugh
authors.forename: O
authors.initials: O
authors.lastname: Tighe
authors.forename: P
authors.initials: P
authors.lastname: Mayne
authors.forename: C
authors.initials: C
authors.lastname: O'Neill
authors.forename: E
authors.initials: E
authors.lastname: Naughten
authors.forename: D T
authors.initials: DT
authors.lastname: Croke
mesh_terms: D015331:Cohort Studies; D017931:DNA Primers; D005693:Galactosemias / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D006801:Humans; D007231:Infant, Newborn; D007494:Ireland; D009154:Mutation; D015997:Neonatal Screening; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase / Q000172:deficiency / Q000235:genetics*
chemical_list: D017931:DNA Primers; D005694:UTP-Hexose-1-Phosphate Uridylyltransferase