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Brother/sister siblings affected with Hunter disease: evidence for skewed X chromosome inactivation
Author(s) -
Sukegawa Kazuko,
Matsuzaki Tetuo,
Fukuda Seiji,
Masuno Mitsuo,
Fukao Toshiyuki,
Kokuryu Mie,
Iwata Shoko,
Tomatsu Shunji,
Orii Tadao,
Kondo Naomi
Publication year - 1998
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/j.1399-0004.1998.tb02654.x
Subject(s) - brother , sister , genetics , biology , sibling , chromosome , gene , psychology , developmental psychology , sociology , anthropology
Hunter disease is an X‐linked recessive disorder caused by a deficiency of iduronate‐2‐sulfatase activity. We describe a pair of brother/sister siblings with a typical feature of Hunter disease (mucopolysaccharidosis type II). They had normal karyotypes but a marked deficiency of iduronate‐2‐sulfatase activity in both lymphocytes and fibroblasts. The molecular analysis of the iduronate‐2‐sulfatase gene revealed the R468L(G 1403 → T) substitution in their genes. Although the sister's genomic DNA was heterozygous for the mutant allele, the sister's cDNA was found to be homogeneous for this mutation. The mother was found to be a heterozygote. The analysis of X chromosome inactivation by comparison of the methylation patterns of the androgen‐receptor (AR) gene which was isolated from the sister's fibroblasts and leucocytes revealed a skewed X chromosome inactivation of the paternal allele. These findings indicate that a skewed X chromosome inactivation of the paternal gene and a point mutation in the maternal gene were responsible for the lack of iduronate‐2‐sulfatase activity in the sister.