title: Clinical manifestations of 17 patients affected with mucopolysaccharidosis type VI and eight novel ARSB mutations.
abstract: Mucopolysaccharidosis (MPS) type VI or Maroteaux-Lamy syndrome is a very rare autosomal recessive lysosomal storage disease, caused by a deficiency of the enzyme N-acetylgalactosamine-4-sulfatase (Arylsulfatase B, ARSB). Clinical examination, biochemical studies, and molecular genetic analyses have been performed in 17 patients affected with MPS VI from 15 unrelated families from Thailand, India, and Turkey. Large ear lobule appears to be a newly recognized finding of this syndrome. Mutation analysis of the ARSB gene revealed seven missense and three frameshift mutations of which eight were novel. Novel missense mutations were p.Asp53Asn, p.Val376Glu, p.Glu390Lys, p.Pro445Leu, and p.Trp450Cys, while an Indian patient was homozygous for two novel missense mutations (p.Pro445Leu and p.Trp450Cys). Three novel frameshift mutations were p.Pro70fsX123, p.Ser403fs, and p.Thr526fs. Two previously reported mutations, p.Arg160Gln and p.Leu321Pro, were also observed in our cohort. The amino acid Arg160 appears to be the mutational hot spot for the ARSB gene. Five patients homozygous for p.Leu321Pro mutation had early onset of the disease, and haplotype analysis showed that the mutation is a founder mutation in Turkish population.
authors.affiliation: Center of Excellence, Chiang Mai University; Craniofacial Genetics Laboratory, Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand; DENTALAND CLINIC, Chiang Mai, Thailand.
authors.forename: Piranit Nik
authors.initials: PN
authors.lastname: Kantaputra
authors.forename: Hulya
authors.initials: H
authors.lastname: Kayserili
authors.forename: Yeliz
authors.initials: Y
authors.lastname: Guven
authors.forename: Warissara
authors.initials: W
authors.lastname: Kantaputra
authors.forename: Mehmet C
authors.initials: MC
authors.lastname: Balci
authors.forename: Pranoot
authors.initials: P
authors.lastname: Tanpaiboon
authors.forename: Napaporn
authors.initials: N
authors.lastname: Tananuvat
authors.forename: Anusha
authors.initials: A
authors.lastname: Uttarilli
authors.forename: Ashwin
authors.initials: A
authors.lastname: Dalal
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D005260:Female; D016368:Frameshift Mutation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007194:India / Q000453:epidemiology; D007493:Iraq / Q000453:epidemiology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009087:Mucopolysaccharidosis VI / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D020125:Mutation, Missense; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000235:genetics*; D017510:Protein Folding; D057165:Proteostasis Deficiencies / Q000235:genetics; D014421:Turkey / Q000453:epidemiology; D055815:Young Adult
chemical_list: D020051:N-Acetylgalactosamine-4-Sulfatase; C581941:ARSB protein, human
keywords: ARSB; MPS VI; Maroteaux-Lamy syndrome; dermatan sulfate; genotype-phenotype correlation; hoarse voice; large ear lobule