CLINICAL REPORT A Mother and Daughter With the p.R443X Mutation of Mucopolysaccharidosis Type II: Genotype and Phenotype Analysis Young Bae Sohn, 1 Su Jin Kim, 1 Sung Won Park, 1 Hyung-Doo Park, 2 Chang-Seok Ki, 2 Chi Hwa Kim, 3 Seung Won Huh, 3 Sunghee Yeau, 4 Kyung-Hoon Paik, 1 and Dong-Kyu Jin 3 * 1 Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea 2 Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea 3 Clinical Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea 4 Department of Science Education, Ewha Womans University, Seoul, Korea Received 11 July 2009; Accepted 1 June 2010 Mucopolysaccharidosis type II (Hunter syndrome) is a lysosomal storage disease caused by a deficiency of iduronate-2-sulfatase. Most reported patients are males because of X-linked recessive inheritance pattern. Only a few female patients with Hunter syndrome have been reported, and there is no prior report of offspring from a patient with Hunter syndrome. In this report, we describe a woman with mild manifestations of Hunter syndrome who gave birth to a daughter. Both the mother and daughter carried the p.R443X mutation in exon 9 of the ID2S gene. Iduronate-2-sulfatase activity in the mother was as low as that found in male Hunter syndrome patients, but it was in the low-normal range in her daughter. Unlike her mother, the daughter did not show any physical signs of Hunter syndrome, and urinary excretion of glycosaminoglycan was within normal range. However, she had severe pulmonary vein stenosis with pulmonary hypertension and a large atrial septal defect and died at 11 months of age. Ó 2010 Wiley-Liss, Inc. Key words: mucopolysaccharidosis type II; female Hunter syndrome; genotype; phenotype; enzyme replacement therapy INTRODUCTION Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is a lysosomal storage disease caused by a deficiency of iduronate-2- sulfatase. Most reported patients are males because of the X-linked recessive inheritance pattern [Neufeld and Muenzer, 2001]. Here, we describe the case of a woman with Hunter syndrome who gave birth to a heterozygote daughter and discuss the relevant issues. CLINICAL REPORT A 28-year-old woman (index case) was referred our clinic, for the evaluation of coarse facial features and short stature. The family history was notable for an older brother who was diagnosed with MPS II, and died at 25 years of age. The index case was born from healthy and nonconsanguineous Korean parents; she had short stature (148 cm, À3.5 SD), coarse facial features, a short neck and mild mental retardation, suggesting the possibility of Hunter syndrome. Her tongue was not enlarged. There was no hearing impairment. On auscultation, no cardiac murmur was detected. There was no hepatosplenomegaly or joint contractures. The skeletal X-rays did not show multiplex dysostosis, a typical finding of Hunter syndrome. Echocardiography was unremarkable. The diagnosis of a mild type MPS II was confirmed by analysis of iduronate-2-sulfatase enzyme activity in fibroblasts and leukocytes (Table I). Activity of iduronate-2-sulfatase was 1.4 nmol/4 hr/mg protein (reference range, RR, 35.0–80.0) in the fibroblasts and 20.0 nmol/4 hr/mg protein (RR, 25.9–53.5) in the leukocytes. The enzyme assays in the patient were performed at the Munich Grant sponsor: Korea Healthcare Technology R&D Project; Grant sponsor: Ministry for Health, Welfare and Family Affairs, Republic of Korea; Grant number: A080588; Grant sponsor: Samsung Biomedical Research Institute; Grant numbers: C-A6-227-3, C-A9-240-2. *Correspondence to: Dr. Dong-Kyu Jin, Department of Pediatrics, Samsung Medical Center, 50 Il-Won Dong, Gang-Nam Gu, Seoul 135-710, Republic of Korea. E-mail: jindk@skku.edu Published online 16 November 2010 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ajmg.a.33589 How to Cite this Article: Sohn YB, Kim SJ, Park SW, Park H-D, Ki C-S, Kim CH, Huh SW, Paik K-H, Jin D-K. 2010. A mother and daughter with the p.R443X mutation of mucopolysaccharidosis type II: Genotype and phenotype analysis. Am J Med Genet Part A 152A:3129–3132. Ó 2010 Wiley-Liss, Inc. 3129