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Simultaneous occurrence of various mutations and polymorphisms in cis and in trans of the galactose-1-phosphate uridyltransferase gene in a Turkish family with classical galactosemia.
J Mol Med (Berl). 1998 Sep; 76(10):715-9.JM

Abstract

Classical galactosemia, characterized clinically by acute hepatic dysfunction, sepsis, cataract, and failure to thrive, is caused by deficiency of galactose-1-phosphate uridyltransferase (GALT). Galactose restriction normalizes these acute symptoms; however, long-term complications such as intellectual deficits and ovarian failure are conspicuous in the majority of patients. Here we report two Turkish siblings with classical galactosemia. The clinical course of the two children differed markedly: only the older girl suffered from severe acute symptoms during the neonatal period, and she developed greater mental retardation than her younger affected brother. The functional activity of GALT was virtually absent in each affected children. The mother and two healthy siblings exhibited approximately 50% normal GALT activity and the father approximately 25%. Molecular analysis revealed that these two galactosemic siblings were homozygous for a stop codon mutation of E340X in GALT exon 10. Moreover, two additional mutations, a neutral polymorphism L218L and N314D, which are typical for the Duarte-I variant, were found in the same GALT allele. The two healthy siblings and the parents were heterozygous for these combinations of mutations. In addition, the father's second GALT allele revealed three intron mutations at nucleotide position 1105 (G-->C), 1323 (G-->A) and 1391 (G-->A) and the N314D mutation, which correspond to the mutations of Duarte-2 variant. Our findings indicate that in classical galactosemia several distinct mutations can be present in one allele (in cis) of the GALT gene. Therefore it seems to be necessary to examine all introns and exons of the GALT gene in galactosemic patients who do not carry the Q188R mutation or another frequent mutation in the GALT gene.

Authors+Show Affiliations

Children's Hospital, University of Würzburg, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9766850

Citation

Schuster, V, et al. "Simultaneous Occurrence of Various Mutations and Polymorphisms in Cis and in Trans of the Galactose-1-phosphate Uridyltransferase Gene in a Turkish Family With Classical Galactosemia." Journal of Molecular Medicine (Berlin, Germany), vol. 76, no. 10, 1998, pp. 715-9.
Schuster V, Podskarbi T, Ottensmeier H, et al. Simultaneous occurrence of various mutations and polymorphisms in cis and in trans of the galactose-1-phosphate uridyltransferase gene in a Turkish family with classical galactosemia. J Mol Med (Berl). 1998;76(10):715-9.
Schuster, V., Podskarbi, T., Ottensmeier, H., Haubner, M., & Shin, Y. S. (1998). Simultaneous occurrence of various mutations and polymorphisms in cis and in trans of the galactose-1-phosphate uridyltransferase gene in a Turkish family with classical galactosemia. Journal of Molecular Medicine (Berlin, Germany), 76(10), 715-9.
Schuster V, et al. Simultaneous Occurrence of Various Mutations and Polymorphisms in Cis and in Trans of the Galactose-1-phosphate Uridyltransferase Gene in a Turkish Family With Classical Galactosemia. J Mol Med (Berl). 1998;76(10):715-9. PubMed PMID: 9766850.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simultaneous occurrence of various mutations and polymorphisms in cis and in trans of the galactose-1-phosphate uridyltransferase gene in a Turkish family with classical galactosemia. AU - Schuster,V, AU - Podskarbi,T, AU - Ottensmeier,H, AU - Haubner,M, AU - Shin,Y S, PY - 1998/10/10/pubmed PY - 1998/10/10/medline PY - 1998/10/10/entrez SP - 715 EP - 9 JF - Journal of molecular medicine (Berlin, Germany) JO - J Mol Med (Berl) VL - 76 IS - 10 N2 - Classical galactosemia, characterized clinically by acute hepatic dysfunction, sepsis, cataract, and failure to thrive, is caused by deficiency of galactose-1-phosphate uridyltransferase (GALT). Galactose restriction normalizes these acute symptoms; however, long-term complications such as intellectual deficits and ovarian failure are conspicuous in the majority of patients. Here we report two Turkish siblings with classical galactosemia. The clinical course of the two children differed markedly: only the older girl suffered from severe acute symptoms during the neonatal period, and she developed greater mental retardation than her younger affected brother. The functional activity of GALT was virtually absent in each affected children. The mother and two healthy siblings exhibited approximately 50% normal GALT activity and the father approximately 25%. Molecular analysis revealed that these two galactosemic siblings were homozygous for a stop codon mutation of E340X in GALT exon 10. Moreover, two additional mutations, a neutral polymorphism L218L and N314D, which are typical for the Duarte-I variant, were found in the same GALT allele. The two healthy siblings and the parents were heterozygous for these combinations of mutations. In addition, the father's second GALT allele revealed three intron mutations at nucleotide position 1105 (G-->C), 1323 (G-->A) and 1391 (G-->A) and the N314D mutation, which correspond to the mutations of Duarte-2 variant. Our findings indicate that in classical galactosemia several distinct mutations can be present in one allele (in cis) of the GALT gene. Therefore it seems to be necessary to examine all introns and exons of the GALT gene in galactosemic patients who do not carry the Q188R mutation or another frequent mutation in the GALT gene. SN - 0946-2716 UR - https://www.unboundmedicine.com/medline/citation/9766850/Simultaneous_occurrence_of_various_mutations_and_polymorphisms_in_cis_and_in_trans_of_the_galactose_1_phosphate_uridyltransferase_gene_in_a_Turkish_family_with_classical_galactosemia_ L2 - http://www.diseaseinfosearch.org/result/2973 DB - PRIME DP - Unbound Medicine ER -