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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Barbouth D, Slepak T, Klapper H, Lai K, Elsas LJ (2006) Prevention of a molecular misdiagnosis in galactosemia. Genet Med 8:178–182
Bosch AM (2006) Classical galactosemia revisited. J Inherit Metab Dis 29:516–525
Calderon FR, Phansalkar AR, Crockett DK, Miller M, Mao R (2007) Mutation database for the galactose-1-phosphate uridyltransferase (GALT) gene. Hum Mutat 28:939–943
Carney AE, Sanders RD, Garza KR, McGaha LA, Bean LJ, Coffee BW, Thomas JW, Cutler DJ, Kurtkaya NL, Fridovich-Keil JL (2009) Origins, distribution and expression of the Duarte-2 (D2) allele of galactose-1-phosphate uridyltransferase. Hum Mol Genet 18:1624–1632
Coffee B, Hjelm LN, DeLorenzo A, Courtney EM, Yu C, Muralidharan K (2006) Characterization of an unusual deletion of the galactose-1-phosphate uridyl transferase (GALT) gene. Genet Med 8:635–640
Elsas LJ 2nd, Lai K (1998) The molecular biology of galactosemia. Genet Med 1:40–48
Ficicioglu C, Hussa C, Gallagher PR, Thomas N, Yager C (2010) Monitoring of biochemical status in children with Duarte galactosemia: utility of galactose, galactitol, galactonate, and galactose 1-phosphate. Clin Chem 56:1177–1182
Trbusek M, Francová H, Kozák L (2001) Galactosemia: deletion in the 5′ upstream region of the GALT gene reduces promoter efficiency. Hum Genet 109:117–120
Velázquez-Aragón J, Alcántara-Ortigoza MA, Vela-Amieva M, Monroy S, Martínez-Cruz V, Todd-Quiñones C, González-Del Angel A (2008) Low allelic heterogeneity in a sample of Mexican patients with classical galactosaemia. J Inherit Metab Dis. [Epub ahead of print] DOI 10.1007/s10545-008-0905-y
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Additional information
Communicated by: Gerard T. Berry.
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.
Rights and permissions
Copyright information
© 2011 SSIEM and Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Angel, A.Gd., Velázquez-Aragón, J., Alcántara-Ortigoza, M.A., Vela-Amieva, M., Hernández-Martínez, N. (2011). Phenotype–Genotype Discrepancy Due to a 5.5-kb Deletion in the GALT Gene. In: JIMD Reports - Case and Research Reports, 2011/2. JIMD Reports, vol 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2011_30
Download citation
DOI: https://doi.org/10.1007/8904_2011_30
Received:
Revised:
Accepted:
Published:
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-24757-6
Online ISBN: 978-3-642-24758-3
eBook Packages: MedicineMedicine (R0)