Human β-mannosidase cDNA characterization and first identification of a mutation associated with human β-mannosidosis

Aisha H. Alkhayat, Stacey A. Kraemer, Jeffrey R. Leipprandt, Milan Macek, Wim J. Kleijer, Karen H. Friderici

Research output: Contribution to journalArticle

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Abstract

Human β-mannosidosis is an autosomal recessive, lysosomal storage disease caused by a deficiency of the enzyme β-mannosidase. Unlike the severe clinical manifestation of the disease in ruminants, in which it leads to neonatal death, the human disease phenotype is generally milder. In addition, the phenotypic manifestation among the reported cases of human β-mannosidosis is variable, even among members of the same family. To understand the molecular basis of the human disease and the mechanisms for such clinical variability, we sequenced the entire coding region of the human β-mannosidase gene using a combination of cDNA library screening, RT-PCR and 5' rapid amplification of cDNA ends (RACE). The composite cDNA is 3293 nt, consisting of an 87 nt 5'-untranslated region, 2640 nt coding region and 566 nt 3'-untranslated region. The gene was localized to human chromosome 4q22-25. Analysis of a multiple tissue northern blot demonstrated a single 3.7 kb transcript. Mutation analysis of a Czech gypsy family with two siblings differently affected with β-mannosidosis demonstrated a homozygous A→G transition 2 bp upstream of a splice acceptor site. The associated cryptic splice site activation and exon skipping caused by this mutation resulted in two abnormally spliced mutant mRNA species in both siblings.

Original languageEnglish
Pages (from-to)75-83
Number of pages9
JournalHuman Molecular Genetics
Volume7
Issue number1
DOIs
Publication statusPublished - Jan 1998

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Mannosidase Deficiency Diseases
Mannosidases
Complementary DNA
Mutation
RNA Splice Sites
Siblings
Roma
Lysosomal Storage Diseases
5' Untranslated Regions
Ruminants
Human Chromosomes
3' Untranslated Regions
Gene Library
Northern Blotting
Genes
Exons
Phenotype
Polymerase Chain Reaction
Messenger RNA
Enzymes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Human β-mannosidase cDNA characterization and first identification of a mutation associated with human β-mannosidosis. / Alkhayat, Aisha H.; Kraemer, Stacey A.; Leipprandt, Jeffrey R.; Macek, Milan; Kleijer, Wim J.; Friderici, Karen H.

In: Human Molecular Genetics, Vol. 7, No. 1, 01.1998, p. 75-83.

Research output: Contribution to journalArticle

Alkhayat, Aisha H. ; Kraemer, Stacey A. ; Leipprandt, Jeffrey R. ; Macek, Milan ; Kleijer, Wim J. ; Friderici, Karen H. / Human β-mannosidase cDNA characterization and first identification of a mutation associated with human β-mannosidosis. In: Human Molecular Genetics. 1998 ; Vol. 7, No. 1. pp. 75-83.
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