Galactosaemia and allelic variation at the galactose-1-phosphate uridyltransferase gene: a complex relationship between genotype and phenotype

Abstract

Allelic variation at the galactose-1-phosphate uridyltransferase gene undoubtedly plays a role in defining the biochemical and clinical phenotype. However, clinical galactosaemia is a complex trait in which multiple developmental and metabolic pathways are involved. Ultimately the phenotype is beyond the control of the single gene itself.

Molecular and clinical analysis of patients with classic and Duarte galactosemia in western Hungary

“…p.Q188R was also found to be the most frequent mutation in the present study in the Hungarian population: of 80 alleles studied we found 36 alleles carrying this mutation (45%). Our finding agrees with observations that the relative frequency of p.Q188R mutation decreases from west to east and from north to south in the European continent [11][12][13][14][23][24][25][26][27].…”

“…We detected this mutation in 25 out of 80 alleles (31.2%). Unlike p.Q188R, this alteration shows increasing frequency across the continent towards the east [12][13][14][23][24][25][26][27].…”

Introduction to the Maastricht workshop: lessons from the past and new directions in galactosemia

“…Soon thereafter, many causative gene mutations were identified producing a heterogeneous array of impaired pGALT function (Elsas and Lai 1998;Tyfield 2000;Calderon et al 2007).…”

Newborn Screening for Galactosemia in the United States: Looking Back, Looking Around, and Looking Ahead

“…However, not all mutations in GALT are functional nulls; many are "hypomorphs," mutations that leave some residual activity intact (e.g., (Riehman et al 2001)). Indeed, one extremely mild variant called the Duarte (D or D2) allele is associated with about half of the normal level of GALT activity (Carney et al 2009;Elsas et al 2001;Greber et al 1995;Levy et al 1978;Mellman et al 1968;Podskarbi et al 1996;Tighe et al 2004;Trbusek et al 2001;Tyfield 2000). Worldwide, D2 alleles are found at an allele frequency of >11% in Europeans, less than 3% in Asians, and almost zero in Africans (http://hapmap.ncbi.nlm.…”