Journal Article

α-Mannosidosis:Functional Cloning of the Lysosomal α-Mannosidase cDNA and Identification of a Mutation in Two Affected Siblings

Øivind Nilssen, Thomas Berg, Hilde M. F. Riise, Umayal Ramachandran, Gry Evjen, Gaute M. Hansen, Dag Malm, Lisbeth Tranebjaerg and Ole K. Tollersrud

in Human Molecular Genetics

Volume 6, issue 5, pages 717-726
Published in print May 1997 | ISSN: 0964-6906
Published online May 1997 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/6.5.717
α-Mannosidosis:Functional Cloning of the Lysosomal α-Mannosidase cDNA and Identification of a Mutation in Two Affected Siblings

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α-Mannosidosis (MIM 248500) is an autosomal recessive lysosomal storage disorder resulting from deficient activity of lysosomal α-mannosidase (LAMAN) (EC 3.2.1.24). The disease is characterized by massive intracellular accumulation of mannose-rich oligosaccharides with resulting mental retardation, hearing loss, immune deficiency and skeletal changes. We report here the purification and characterization of human placenta LAMAN. The enzyme is synthesized as a single-chain precursor which is processed into three glycopeptides of 70, 42 and 15 kDa. The 70 kDa peptide is further partially proteolysed into three more peptides that are joined by disulfide bridges. The laman cDNA sequence was assembled from overlapping fragments obtained by PCR on human fibroblast and human lung cDNA. The deduced amino acid sequence contains a putative signal peptide of 48 amino acids followed by a polypeptide sequence of 962 amino acids. Northern blot analyses revealed a single transcript of ∼3.5 kb present in all tissues examined but at varying levels. Two affected siblings of Palestinian origin were homozygous for a mutation that causes a His→Leu replacement at a position which is conserved among class 2α-mannosidases from several species.

Journal Article.  6167 words.  Illustrated.

Subjects: Genetics and Genomics

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