ß 2008 Wiley-Liss, Inc. American Journal of Medical Genetics Part A 146A:1736–1740 (2008) Clinical Report Novel b-Galactosidase Gene Mutation p.W273R in a Woman With Mucopolysaccharidosis Type IVB (Morquio B) and Lack of Response to in vitro Chaperone Treatment of Her Skin Fibroblasts Zoran S. Gucev, 1 * Velibor Tasic, 1 Aleksandra Jancevska, 1 Georgi Zafirovski, 1 Ivo Kremensky, 2 Ivanka Sinigerska, 2 Eiji Nanba, 3 Katsumi Higaki, 3 Filip Gucev, 1 and Yoshiyuki Suzuki 4 1 Medical Faculty Skopje, Skopje, Macedonia 2 National Genetic Laboratory, Sofia, Bulgaria 3 Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University, Yonago, Japan 4 International University of Health and Welfare Graduate School, Otawara, Japan Received 1 August 2007; Accepted 19 February 2008 The patient is a 24-year-old woman who first came for consultation at age 10 years. Based on clinical phenotype and thin-layer chromatography of urinary oligosaccharides, peripheral leukocytes were sent for b-galactosidase assay. This testing showed a deficiency in enzyme activity, and gene mutation analysis identified a previously reported mutation p.H281Y (875C > T) and a novel mutation p.W273R (817T > C). Unlike previously reported patients, mutant enzymes in this patient’s cultured skin fibroblasts did not respond to treatment with a chaperone compound, N-octyl-4-epi-b-valienamine. ß 2008 Wiley-Liss, Inc. Key words: Morquio B disease; b-galactosidase; gene mutation; compound heterozygote; Macedonian How to cite this article: Gucev ZS, Tasic V, Jancevska A, Zafirovski G, Kremensky I, Sinigerska I, Nanba E, Higaki K, Gucev F, Suzuki Y. 2008. Novel b-galactosidase gene mutation p.W273R in a woman with mucopolysaccharidosis type IVB (Morquio B) and lack of response to in vitro chaperone treatment of her skin fibroblasts. Am J Med Genet Part A 146A:1736 – 1740. INTRODUCTION Mucopolysaccharidosis (MPS) IVB (OMIM# 253010) is a rare autosomal recessive disease [Suzuki et al., 2001] characterized by short-trunk dwarfism, and progressive and generalized skeletal dysplasia. Life threatening atlanto-axial subluxation may occur as a result of the instability of the odontoid process and ligamentous laxity. Genu valgus and kyphosis with short trunk and short neck are early signs of the disease. Fine corneal deposits, hepatomegaly, small teeth with thin enamel, frequent caries formation and cardiac valvular lesions are extra-skeletal abnor- malities. Intelligence is preserved. The disease is caused by b-galactosidase deficiency, resulting in keratin sulphate and oligosaccharide storage in the skeletal system and connective tissue, with normal catalytic activity for ganglioside G M1 . Several mutations of the b-galactosidase gene have been found in Morquio B patients. However, less than 30 Morquio B patients have been characterized for their respective DNA mutations [Santamaria et al., 2006]. CLINICAL REPORT The patient is a 24-year-old Macedonian girl who first came for consultation for growth delay at the age of 10 years. Her intelligence was normal. Her final height was 138 cm. She progressively devel- oped distinctive facial features with a broad mouth and a short nose with anteverted nares. Hearing was Grant sponsor: Ministry of Education, Culture, Science, Sports, and Technology of Japan; Grant numbers: 13680918, 14207106; Grant sponsor: Ministry of Health, Labour and Welfare of Japan; Grant numbers: H10-No-006, H14-Kokoro-017, H17-Kokoro-019. *Correspondence to: Zoran S. Gucev, Medical Faculty Skopje, 50 Divizija BB, 1000 Skopje, Macedonia. E-mail: gucevz@gmail.com DOI 10.1002/ajmg.a.32318