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Hunter disease in a girl caused by R468Q mutation in the iduronate-2-sulfatase gene and skewed inactivation of the X chromosome carrying the normal allele.
Hum Mutat 1997; 10(5):361-7HM

Abstract

Hunter disease is an X-linked recessive mucopolysaccharide storage disorder caused by iduronate-2-sulfatase deficiency and is rare in females. We describe here findings in a girl with Hunter disease of the severe type. She had a normal karyotype but a marked deficiency of iduronate-2-sulfatase activity in lymphocytes and cultured fibroblasts. In a sequence analysis of the iduronate-2-sulfatase gene, evidence was obtained for the R468Q (G1403 to A) mutation, a common one in Hunter disease. RT-PCR showed her cDNA to represent only the R468Q allele, although at the genomic level she was a heterozygote with one normal allele. Her brother had the R468Q mutation, and their mother was a carrier of this mutation. The fusion products of CHO (TG(R),Neo(R)) with patient's fibroblasts cultured in HAT/G418 selective medium, carried only the maternal allele. However, in genomic DNA from the patient's fibroblasts, only the paternal allele of the androgen receptor gene, a gene subjected to differential methylation of the inactive X-chromosome, was methylated. These findings strongly suggest that the severe form of Hunter disease in this girl was the result of selective expression of the maternal allele carrying the missense mutation R468Q, which in turn resulted from skewed X inactivation of the paternal nonmutant X chromosome.

Authors+Show Affiliations

Department of Pediatrics, Gifu University School of Medicine, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9375851

Citation

Sukegawa, K, et al. "Hunter Disease in a Girl Caused By R468Q Mutation in the Iduronate-2-sulfatase Gene and Skewed Inactivation of the X Chromosome Carrying the Normal Allele." Human Mutation, vol. 10, no. 5, 1997, pp. 361-7.
Sukegawa K, Song XQ, Masuno M, et al. Hunter disease in a girl caused by R468Q mutation in the iduronate-2-sulfatase gene and skewed inactivation of the X chromosome carrying the normal allele. Hum Mutat. 1997;10(5):361-7.
Sukegawa, K., Song, X. Q., Masuno, M., Fukao, T., Shimozawa, N., Fukuda, S., ... Orii, T. (1997). Hunter disease in a girl caused by R468Q mutation in the iduronate-2-sulfatase gene and skewed inactivation of the X chromosome carrying the normal allele. Human Mutation, 10(5), pp. 361-7.
Sukegawa K, et al. Hunter Disease in a Girl Caused By R468Q Mutation in the Iduronate-2-sulfatase Gene and Skewed Inactivation of the X Chromosome Carrying the Normal Allele. Hum Mutat. 1997;10(5):361-7. PubMed PMID: 9375851.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hunter disease in a girl caused by R468Q mutation in the iduronate-2-sulfatase gene and skewed inactivation of the X chromosome carrying the normal allele. AU - Sukegawa,K, AU - Song,X Q, AU - Masuno,M, AU - Fukao,T, AU - Shimozawa,N, AU - Fukuda,S, AU - Isogai,K, AU - Nishio,H, AU - Matsuo,M, AU - Tomatsu,S, AU - Kondo,N, AU - Orii,T, PY - 1997/1/1/pubmed PY - 2000/6/22/medline PY - 1997/1/1/entrez SP - 361 EP - 7 JF - Human mutation JO - Hum. Mutat. VL - 10 IS - 5 N2 - Hunter disease is an X-linked recessive mucopolysaccharide storage disorder caused by iduronate-2-sulfatase deficiency and is rare in females. We describe here findings in a girl with Hunter disease of the severe type. She had a normal karyotype but a marked deficiency of iduronate-2-sulfatase activity in lymphocytes and cultured fibroblasts. In a sequence analysis of the iduronate-2-sulfatase gene, evidence was obtained for the R468Q (G1403 to A) mutation, a common one in Hunter disease. RT-PCR showed her cDNA to represent only the R468Q allele, although at the genomic level she was a heterozygote with one normal allele. Her brother had the R468Q mutation, and their mother was a carrier of this mutation. The fusion products of CHO (TG(R),Neo(R)) with patient's fibroblasts cultured in HAT/G418 selective medium, carried only the maternal allele. However, in genomic DNA from the patient's fibroblasts, only the paternal allele of the androgen receptor gene, a gene subjected to differential methylation of the inactive X-chromosome, was methylated. These findings strongly suggest that the severe form of Hunter disease in this girl was the result of selective expression of the maternal allele carrying the missense mutation R468Q, which in turn resulted from skewed X inactivation of the paternal nonmutant X chromosome. SN - 1059-7794 UR - https://www.unboundmedicine.com/medline/citation/9375851/Hunter_disease_in_a_girl_caused_by_R468Q_mutation_in_the_iduronate_2_sulfatase_gene_and_skewed_inactivation_of_the_X_chromosome_carrying_the_normal_allele_ L2 - https://doi.org/10.1002/(SICI)1098-1004(1997)10:5<361::AID-HUMU5>3.0.CO;2-I DB - PRIME DP - Unbound Medicine ER -