title: Angiokeratoma corporis diffusum in human beta-mannosidosis: Report of a new case and a novel mutation.
abstract: BACKGROUND
  Human beta-mannosidosis, a rare disorder of oligosaccharide catabolism, results from a deficiency of beta-mannosidase activity. So far, mutational analysis has been performed in only seven families and revealed 11 mutations in the MANBA gene which encodes the enzyme beta-mannosidase.
  
  
  OBJECTIVE
  We report here a 36-year-old Arab female with beta-mannosidosis who presented with mental retardation and multiple angiokeratomas. We describe in this patient a novel null mutation and review the previously reported MANBA gene mutations and their clinical correlations.
  
  
  METHODS
  Histopathology, ultrastructural analysis, and enzyme assays were performed. Sequencing of cDNA and genomic DNA analysis was conducted in a search for a mutation in the MANBA gene.
  
  
  RESULTS
  Histopathology of a skin biopsy specimen from the patient showed the characteristic findings of angiokeratoma. Electron microscopy showed cytoplasmic vacuolation. Enzymatic activity of beta-mannosidase in the patient's serum, leukocytes, and fibroblasts was less than 1% of control values. Sequencing of the MANBA cDNA revealed a G-->A transition in exon 6 at nucleotide position c.693, resulting in the formation of a stop codon (W231X).
  
  
  CONCLUSIONS
  Only one family was studied.
  
  
  CONCLUSIONS
  A new case of human beta-mannosidosis is presented and the first MANBA gene mutation from Arab ancestry is reported. Reviewing the reported MANBA gene mutations does not reveal a clear genotype-phenotype correlation. The importance of angiokeratoma corporis diffusum as the clue to the diagnosis of beta-mannosidosis and other lysosomal storage diseases is emphasized.
authors.affiliation: Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem 91120, Israel.
authors.forename: Vered
authors.initials: V
authors.lastname: Molho-Pessach
authors.forename: Ruth
authors.initials: R
authors.lastname: Bargal
authors.forename: Yigal
authors.initials: Y
authors.lastname: Abramowitz
authors.forename: Victoria
authors.initials: V
authors.lastname: Doviner
authors.forename: Arieh
authors.initials: A
authors.lastname: Ingber
authors.forename: Annick
authors.initials: A
authors.lastname: Raas-Rothschild
authors.forename: Zvi
authors.initials: Z
authors.lastname: Ne'eman
authors.forename: Marsha
authors.initials: M
authors.lastname: Zeigler
authors.forename: Abraham
authors.initials: A
authors.lastname: Zlotogorski
mesh_terms: D000225:Adenine; D000328:Adult; D018912:Arabs / Q000235:genetics*; D001483:Base Sequence; D018389:Codon, Nonsense; D018388:Codon, Terminator; D003593:Cytoplasm / Q000648:ultrastructure; D005091:Exons; D000795:Fabry Disease / Q000209:etiology* / Q000473:pathology; D005260:Female; D006147:Guanine; D006801:Humans; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D012867:Skin / Q000473:pathology; D014617:Vacuoles / Q000648:ultrastructure; D044902:beta-Mannosidase / Q000235:genetics*; D044905:beta-Mannosidosis / Q000150:complications* / Q000235:genetics*
chemical_list: D018389:Codon, Nonsense; D018388:Codon, Terminator; D006147:Guanine; D044902:beta-Mannosidase; D000225:Adenine