Disease relevance of ALG9

• The ALG9 defect found in the patient with CDG--who presented with developmental delay, hypotonia, seizures, and hepatomegaly--shows that efficient lipid-linked oligosaccharide synthesis is required for proper human development and physiology [1].
• Inborn ALG9 deficiency (congenital disorders of glycosylation type IL) is associated with progressive microcephaly, seizures, developmental delay, and hepatomegaly [2].

Psychiatry related information on ALG9

• It is unknown whether common variations of ALG9 predispose to bipolar affective disorder [2].
• Gene content analyses of the breakpoint junctions revealed disruption of a gene (DIBD1 ) at 11q23, a genomic region that has also been implicated in schizophrenia and Tourette syndrome [3].

High impact information on ALG9

• Using this approach, we have found, in a patient with CDG, a deficiency of the ALG9 alpha 1,2 mannosyltransferase enzyme, which causes an accumulation of lipid-linked-GlcNAc(2)Man(6) and -GlcNAc(2)Man(8) structures, which was paralleled by the transfer of incomplete oligosaccharides precursors to protein [1].
• Identification and functional analysis of a defect in the human ALG9 gene: definition of congenital disorder of glycosylation type IL [1].
• A homozygous point-mutation 1567G-->A (amino acid substitution E523K) was detected in the ALG9 gene [1].
• These analyses overall failed to support a role for DIBD1 in disease susceptibility [3].
• In vivo competition studies against (R,R)-[125I]IQNB indicate that DIBD crosses the blood brain barrier (BBB) [4].

Biological context of ALG9

• RESULTS: We identified three common and distinct haplotypes spanning the ALG9 gene [2].
• METHODS: We tested five polymorphic markers spanning ALG9 (three intragenic and one upstream microsatellite repeats and one common missense variation, V289I (rs10502151) for their association with bipolar I disorder in two pedigree series [2].
• ABSTRACT: BACKGROUND: A mannosyltransferase gene (ALG9, DIBD1) at chromosome band 11q23 was previously identified to be disrupted by a balanced chromosomal translocation t(9;11)(p24;q23) co-segregating with bipolar affective disorder in a small family [2].

Anatomical context of ALG9

• A defect in the ALG9 enzyme was suggested by the accumulation of the DolPP-GlcNAc2Man6 and DolPP-GlcNAc2Man8 in the patient's fibroblasts and confirmed by mutation analysis: the patient is homozygous for the ALG9 mutation p.Y286C [5].
• We conclude that a suitably radiolabeled derivative of DIBD may be of potential use in emission tomographic study of changes in m2 receptors in the central nervous system [4].
• In vitro competition studies against [3H](R)-3-quinuclidinylbenzilate ([3H]QNB) and [3H]N-methylscopolamine ([3H]NMS), using membranes derived from transfected cells expressing only m1, m2, m3, or m4 receptor subtypes, indicate that DIBD is selective for m2/m4 over m1/m3 [4].

Analytical, diagnostic and therapeutic context of ALG9

• In vivo rat brain dissection studies of the competition of PBID or DIBD against (R,S)[125I]IQNB or [3H]QNB exhibited a dose-dependent preferential decrease in the binding of the radiotracer in brain regions that are enriched in the m2 muscarinic subtype [6].

References