Genetic basis of transferase-deficient galactosaemia in Ireland and the population history of the Irish Travellers

  title={Genetic basis of transferase-deficient galactosaemia in Ireland and the population history of the Irish Travellers},
  author={M. Murphy and Brian McHugh and Orna Tighe and Philip D. Mayne and Charles O'Neill and Eileen R. Naughten and David T. Croke},
  journal={European Journal of Human Genetics},
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 role of human demographic history in determining the distribution and frequency of transferase-deficient galactosaemia mutations

Haplotype diversity, in conjunction with measures of genetic diversity and of linkage disequilibrium, indicated that Q188R and K285N are European mutations, which were found to be an ancient mutation that originated before the expansion of Homo sapiens out of Africa.

Classic galactosaemia in the Greek Cypriot population: An epidemiological and molecular study

The carrier frequency for classic galactosaemia among Greek Cypriots was estimated to be 1:88, predicting a homozygote incidence of 1:31,000 births, and the Duarte 1 and Duarte 2 variants were found to be present at a frequency of 5.5% and 2.5%, respectively.

Classical galactosemia and mutations at the galactose‐1‐phosphate uridyl transferase (GALT) gene

The considerable genetic heterogeneity documented to date undoubtedly contributes to the phenotypic heterogeneity that is observed in galactosemia and the additional effects of nonallelic variation and other constitutional factors on phenotypesic variability remain to be elucidated.

Negative screening tests in classical galactosaemia caused by S135L homozygosity

SummaryClassical galactosaemia is relatively common in Ireland due to a high carrier rate of the Q188R GALT mutation. It is screened for using a bacterial inhibition assay (BIA) for free galactose. A

The clinical and molecular spectrum of galactosemia in patients from the Cape Town region of South Africa

Carrier frequency data predict a galactosemia incidence of approximately 1/14 400 for black newborns in the Cape Metropole, which is much higher than the current detection rate, and it is thus likely that many patients go undetected.

Novel GALT variations and mutation spectrum in the Korean population with decreased galactose-1-phosphate uridyltransferase activity

Considering the mutation spectrum in Koreans, direct sequence analysis of entire GALT exons is recommended for accurate diagnosis.

The mutation spectrum of hyperphenylalaninaemia in the Republic of Ireland: the population history of the Irish revisited

An analysis of mutant allele distributions in Ulster, Scotland and the rest of Ireland confirmed that Ulster has been a zone of considerable admixture between the Irish and Scottish populations, indicating a proportion of Scottish admixture in Ulster approaching 46%.

Galactosemia in the Turkish population with a high frequency of Q188R mutation and distribution of Duarte-1 and Duarte-2 variations

It is a very important finding that exons 6 and 10 of the GALT gene account for 79% of all mutant alleles in the Turkish population.

The molecular basis of galactosemia - Past, present and future.

Frequencies of Q188R and N314D Mutations and IVS5-24G>A Intron Variation in the Galactose-1-Phosphate Uridyl Transferase (GALT) Gene in the Slovenian Population

A healthy Slovenian population was analyzed for the frequencies of Q188R and N314D mutations, and for the Duarte-2 indicative intronic variation IVS5-24G>A, and results correlate well with those reported for most other healthy Caucasian populations.



Molecular analysis of PKU in Ireland

Results support the hypothesis of a second, independent founding event for the R408W mutation on an RFLP haplotype 1 VNTR‐8 chromsome background in the Irish/Celtic population.

Molecular heterogeneity of classical and duarte galactosemia: Mutation analysis by denaturing gradient gel electrophoresis

It is concluded that the mutations causing galactosemia are highly heterogeneous and that K285N is a second common galactosedmia mutation in the population.

A common mutation associated with the Duarte galactosemia allele.

The N314D mutation is a common allele that probably causes the Duarte GALT biochemical phenotype and occurs in a predominantly Caucasian, nongalactosemic population, with a prevalence of 5.9%.

Molecular basis for Duarte and Los Angeles variant galactosemia.

It is concluded that the codon change N314D in cis with the base-pair transition 1721C-->T produces the LA variant of galactosemia and that this nucleotide change increases GALT activity by increasing GALT protein abundance without increasing transcription or decreasing thermal lability.

Genetic basis of galactosemia

Classic galactosemia is an inborn error of galactose metabolism and results from deficiency of the ubiquitously expressed enzyme galactose‐1‐phosphate uridyltransferase (GALT). Nine missense

Molecular characterization of two galactosemia mutations: correlation of mutations with highly conserved domains in galactose-1-phosphate uridyl transferase.

The data provide further evidence for the heterogeneity of galactosemia at the molecular level, heterogeneity which might be related to the variable clinical outcome observed in this disorder.

Disorders of galactose metabolism

It seems reasonable, therefore, to treat all galactosaemias by rigidly excluding lactose from the diet, although usually this term is reserved for the older and so far much more common galactose-l-P uridyl transferase deficiency.

Recurrence of the R408W mutation in the phenylalanine hydroxylase locus in Europeans.

An examination of the linkage between the R408W mutation and highly polymorphic RFLP, VNTR, and STR haplotypes suggests that recurrence is the most likely mechanism to account for the two different major haplotype associations of R 408W in Europe.

Disorders of Galactose Metabolism

Three inborn errors of Galactose metabolism are known, one for each step in the Leloir pathway of galactose conversion to glucose, and each occurs in both a benign mild form and a severe and crippling form.