Premium
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
Author(s) -
Sukegawa Kazuko,
Song XiangQian,
Masuno Mitsuo,
Fukao Toshiyuki,
Shimozawa Nobuyuki,
Fukuda Seiji,
Isogai Koji,
Nishio Hisahide,
Matsuo Masafumi,
Tomatsu Shunji,
Kondo Naomi,
Orii Tadao
Publication year - 1997
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1997)10:5<361::aid-humu5>3.0.co;2-i
Subject(s) - biology , genetics , hunter syndrome , allele , mucopolysaccharidosis type ii , gene , mutation , girl , skewed x inactivation , disease , x chromosome , x inactivation , medicine , enzyme replacement therapy
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 (G 1403 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. Hum Mutat 10:361–367, 1997. © 1997 Wiley‐Liss, Inc.