Disease relevance of ALMS1

• Subcellular localization of ALMS1 supports involvement of centrosome and basal body dysfunction in the pathogenesis of obesity, insulin resistance, and type 2 diabetes [1].
• Lack of association between gene variants in the ALMS1 gene and Type 2 diabetes mellitus [2].
• ALMS1 localizes to the basal bodies of cilia and plays a role in intracellular trafficking, but the biological functions of ALMS1 and how these relate to the pathogenesis of obesity, diabetes, and infertility remain unclear [3].
• Alström syndrome is a homogeneous autosomal recessive disorder that is characterized by childhood obesity associated with hyperinsulinemia, chronic hyperglycemia and neurosensory deficits [4].
• Alström syndrome is a rare autosomal recessive disorder characterized by pigmentary retinal degeneration, sensorineural hearing loss, childhood obesity, non-insulin-dependent diabetes mellitus, hyperlipidemia and chronic nephropathy [5].

Psychiatry related information on ALMS1

• This appears to be the second family with a new autosomal recessive disorder differing from Alström syndrome by the presence of mental retardation and absence of renal insufficiency [6].

High impact information on ALMS1

• We mapped the 2p13 breakpoint on the maternal allele to a genomic fragment of 1.7 kb which contains exon 4 and the start of exon 5 of a newly discovered gene (ALMS1); we detected a frameshift mutation in the paternal copy of the gene [7].
• ALMS1 is ubiquitously expressed at low levels and does not share significant sequence homology with other genes reported so far [4].
• Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alström syndrome [4].
• We have studied an individual with Alström syndrome carrying a familial balanced reciprocal chromosome translocation (46, XY,t(2;11)(p13;q21)mat) involving the previously implicated critical region [7].
• Alström syndrome (OMIM 203800) is an autosomal recessive disease, characterized by cone-rod retinal dystrophy, cardiomyopathy and type 2 diabetes mellitus, that has been mapped to chromosome 2p13 (refs 1-5) [7].

Chemical compound and disease context of ALMS1

• CONCLUSION: The first overview of serum triglyceride levels in a significant number of reported cases of Alström Syndrome shows an overlap between severe hypertriglyceridaemia and severe hyperinsulinism, but not a direct correlation between the two nor with insulin resistance measured by HOMA [8].
• PARTICIPANTS--Two siblings with Alström syndrome who were referred to the Endocrine Division for evaluation of obesity, growth, and glucose metabolism [9].

Biological context of ALMS1

• To begin this process, we have analyzed the subcellular localization and tissue distribution of ALMS1 by immunofluorescence [1].
• It is also unclear how ALMS1 mutations relate to the characteristic phenotype [10].
• OBJECTIVES: Our objectives were to characterize body composition and metabolic parameters, to establish ALMS1 mutation spectrum of United Kingdom AS patients, and to determine whether a genotype-phenotype correlation exists [10].
• The exons and intron-exon boundaries of ALMS1 were directly sequenced [10].
• Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alström syndrome [7].

Anatomical context of ALMS1

• We show that ALMS1 is widely expressed and localizes to centrosomes and to the base of cilia [1].
• Fibroblasts with disrupted ALMS1 assemble primary cilia and microtubule cytoskeletons that appear normal, suggesting that the Alström syndrome phenotype results from impaired function rather than abnormal development [1].
• In conclusion, Alms1 foz/foz mouse is a new animal model in which to study the pathogenesis of the metabolic and fertility defects of Alström syndrome, including the role of ALMS1 in appetite regulation, pathogenesis of the metabolic syndrome, pancreatic islet physiology, and spermatogenesis [3].

Associations of ALMS1 with chemical compounds

• CONCLUSION: rhGH therapy might have beneficial effects on body composition, liver fat content, lipid profiles, and insulin resistance in Alström syndrome patients, with improvement of the glucose homeostasis [11].
• We designed an artificial liver support system (ALSS) including plasma exchange, charcoal hemoperfusion, plasma bilirubin absorption, charcoal plasma perfusion, hemofiltration and hemodialysis [12].
• METHODS: We conducted a case-control study at a pediatric hospital with 5 patients (age 5-18 years) with Alström syndrome living in Atlantic Canada and 21 age- and sex-matched healthy control subjects [13].
• After each ALSS treatment, the liver function of these patients greatly improved, serum endotoxin and HBV-DNA concentrations were significantly decreased, and the serum concentration of aromatic amino acids (AAA) such as methionine decreased while BCAA/AAA ratio increased [12].

Other interactions of ALMS1

• The importance of seeking ALMS1 mutations in infants with dilated cardiomyopathy [14].
• Although polymorphisms were identified, our results indicate that mutations in the coding region of LBX2 do not account for Alström syndrome in the six kindreds analyzed [15].
• Human DCTN1: genomic structure and evaluation as a candidate for Alström syndrome [16].
• TGFA: exon-intron structure and evaluation as a candidate gene for Alström syndrome [17].
• The NBC4 gene was mapped to chromosome 2p13 and is a new candidate gene for Alstrom syndrome [18].

Analytical, diagnostic and therapeutic context of ALMS1

• AIM: To assess the effect of artificial liver support system (ALSS) on patients with severe viral hepatitis, who were divided into treatment group and control group [19].
• It is anticipated that this new ALSS will not only be of value in cases of fulminant hepatic failure but that it may also play a role in sustaining life for those awaiting liver transplantation [20].
• The methods of ALSS used included plasma exchange, hemoperfusion, hemofiltration, continuous hemodiafiltration (CHDF) [19].
• A rare case of Alström syndrome presenting with rapidly progressive severe dilated cardiomyopathy diagnosed by echocardiography [21].
• The results of endocrinological studies, karyotype analysis, and digital dermatoglyphics supported the clinical diagnosis of the Alström syndrome [22].

References