Phenotype–Genotype Discrepancy Due to a 5.5-kb Deletion in the GALT Gene

Abstract

Classical galactosemia is an autosomal recessive inborn error of metabolism caused by a deficiency of the galactose-1-phosphate uridyltransferase (GALT). More than 200 mutations have been described in the GALT gene. A 5.5-kb GALT deletion, first described in patients of Ashkenazi Jewish ancestry, may lead either to an erroneous genotype assignment of classical galactosemia or to discrepancies with parental genotypes and the expected biochemical phenotype. The presence of the 5.5-kb deletion was examined in 27 Mexican nonrelated families with at least one child with reduced GALT activity in erythrocytes and it was detected in the 5.5% (n=3) of the 54 alleles tested. The first molecular studies in three of our families showed that the genotypes of the parents were inconsistent with those of their children, which were considered initially as homozygous p.N314D-Duarte 2, but after analyzing for the presence of the 5.5-kb deletion, were reassigned as compound heterozygotes [5.5-kb deletion]+[p.N314D-Duarte 2]. Identification of the 5.5-kb deletion in Mexican patients suggests that this mutation might not be exclusive to a given ethnic group and should be tested in other populations, especially when there is a discrepancy between the genotypes of patients and parents or by incongruence between biochemical phenotype and GALT genotype. Establishing a genotype–phenotype correlation for the 5.5-kb GALT deletion and determining the appropriate management will require additional studies in patients with a G/G genotype bearing the 5.5-kb GALT deletion.

Competing interests: None declared.

Appendices

Take Home Message

The 5.5-kb GALT gene deletion was identified in Mexican patients with reduced GALT activity and it was responsible for discrepancies between genotypes of patients and their parents.

References to Electronic Databases

OMIM 230400; Gene symbol GALT; E.C. 2.7.7.12; EntrezGene ID 2592.

Contributions of Individual Authors

José Velázquez-Aragón, Miguel Alcántara-Ortigoza and Ariadna González-del Angel wrote the first draft of the paper. Marcela Vela-Amieva and Ariadna González-del Angel collected the galactosemic patients and clinical data. José Velázquez-Aragón, Miguel Alcántara-Ortigoza, Nancy Hernández Martínez carried out the molecular analysis. José Velázquez-Aragón, Ariadna Gonzalez-del Angel and Miguel Alcántara-Ortigoza analyzed the data. Ariadna González-del Angel and Marcela Vela-Amieva planned, supervised and coordinated the work. All authors contributed to the final version of the paper.

Details of Funding

The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.