Disease relevance of MAN2B1

• Funtional characterization of four novel MAN2B1 mutations causing juvenile onset alpha-mannosidosis [1].
• Our results provide valuable information for the study of the lysosomal storage disease alpha-mannosidosis, an inherited disorder caused by mutations in the MANB gene which encodes the human lysosomal alpha-mannosidase [2].
• A murine mannosidosis model, LAMAN-deficient mice, was examined on a behavioral task battery that included test for neuromotor, exploratory and neurocognitive (spatial learning and memory) abilities, and multivariate statistical analyses were used to identify behavioral and neurocognitive domains that are most heavily affected by LAMAN deficiency [3].
• A total of 43 patients with multiple sclerosis (MS) consecutively admitted to the Multiple Sclerosis Rehabilitation Hospital in Haslev completed a Danish version of the Laman & Lankhorst Questionnaire (LLQ) on quality of life (qol), and the Beck Depression Inventory (BDI) [4].

High impact information on MAN2B1

• alpha-Mannosidosis is an autosomal recessive disorder caused by deficiency of lysosomal alpha-mannosidase (LAMAN) [5].
• Although there were clinical variations among the patients, no significant LAMAN activity could be detected in any of the fibroblast cultures [5].
• To elucidate the molecular mechanism underlying this disease in both types of patients, we have used PCR, followed by either SSCP analysis or direct sequencing, to analyze the 24 exons and intron/exon boundaries of the alpha-mannosidase gene (MANB) from five patients [6].
• Human chromosome mapping of the mannosidase gene confirmed that the functional gene maps to the MANB locus on chromosome 19 [7].
• By using this mutation as a marker, we demonstrate that 1 year post-BMT, the LAMAN genotype of the patient's leukocytes was identical to that of the donor [8].

Biological context of MAN2B1

• The amino acid sequence of the human lysosomal alpha-mannosidase precursor has been deduced by PCR mediated cloning and sequencing of the cDNA [2].
• The cDNA maps proximal to the centromere on chromosome 19q, the same locus as the MANB gene [2].
• We localized the deoxyhypusine synthase gene on a high resolution cosmid/BAC contig map of chromosome 19 to a region in 19p13.2-distal 19p13.1 between MANB and JUNB [9].
• This is the first fungal gene that encodes MANB [10].
• Laman Gray Jr., M.D., of Jewish Hospital in Louisville, KY., is among the surgeons at the forefront of new minimally invasive heart surgery techniques [11].

Anatomical context of MAN2B1

• This study is the first to successfully express the MANB gene in a human and a murine cell line [12].
• Human LAMAN (lysosomal a-mannosidase) was synthesized as a 120 kDa precursor in transfected COS cells [African-green-monkey kidney cells], which was partly secreted as a single-chain form and partly sorted to the lysosomes being subsequently cleaved into three peptides of 70, 40 and 15 kDa respectively [13].

Analytical, diagnostic and therapeutic context of MAN2B1

• The human MANB cDNA gene was demonstrated in the target cells by Southern blot analysis and the expression of the gene was shown by RT-PCR analysis [12].

References