Редактирование: ALMS1 (раздел)

==Publications==

{{medline-entry
|title=A role for Alström syndrome protein, alms1, in kidney ciliogenesis and cellular quiescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/17206865
|abstract=Premature truncation alleles in the [[ALMS1]] gene are a frequent cause of human Alström syndrome. Alström syndrome is a rare disorder characterized by early obesity and sensory impairment, symptoms shared with other genetic diseases affecting proteins of the primary cilium. [[ALMS1]] localizes to centrosomes and ciliary basal bodies, but truncation mutations in Alms1/[[ALMS1]] do not preclude formation of cilia. Here, we show that in vitro knockdown of Alms1 in mice causes stunted cilia on kidney epithelial cells and prevents these cells from increasing calcium influx in response to mechanical stimuli. The stunted-cilium phenotype can be rescued with a 5' fragment of the Alms1 cDNA, which resembles disease-associated alleles. In a mouse model of Alström syndrome, Alms1 protein can be stably expressed from the mutant allele and is required for cilia formation in primary cells. Aged mice developed specific loss of cilia from the kidney proximal tubules, which is associated with foci of apoptosis or proliferation. As renal failure is a common cause of mortality in Alström syndrome patients, we conclude that this disease should be considered as a further example of the class of renal ciliopathies: wild-type or mutant alleles of the Alström syndrome gene can support normal kidney ciliogenesis in vitro and in vivo, but mutant alleles are associated with age-dependent loss of kidney primary cilia.
|mesh-terms=* Abnormalities, Multiple
* Aging
* Animals
* Cell Cycle Proteins
* Cilia
* DNA-Binding Proteins
* Gene Expression Regulation
* Homeostasis
* Humans
* Kidney
* Mechanotransduction, Cellular
* Mice
* Mice, Mutant Strains
* Molecular Sequence Data
* Peptide Fragments
* RNA, Messenger
* RNA, Small Interfering
* Syndrome
* Transcription, Genetic

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1761047
}}
{{medline-entry
|title=Syndromic obesity and diabetes: changes in body composition with age and mutation analysis of [[ALMS1]] in 12 United Kingdom kindreds with Alstrom syndrome.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/16720663
|abstract=Alström syndrome (AS) is a monogenic form of infancy-onset obesity and insulin resistance, caused by [[ALMS1]] mutations. The natural history of the insulin resistance is unknown, in particular how this relates to changes in body composition. It is also unclear how [[ALMS1]] mutations relate to the characteristic phenotype. 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. We conducted a cross-sectional cohort study of 12 unrelated subjects with AS. Age-standardized body composition was assessed by anthropometry and dual-energy x-ray absorptiometry and insulin sensitivity by homeostasis model assessment. The exons and intron-exon boundaries of [[ALMS1]] were directly sequenced. The study was performed during the annual Alström Syndrome UK multidisciplinary screening clinic. AS patients have early-onset obesity, but body mass index, waist circumference, and body fat from dual-energy x-ray absorptiometry were negatively correlated with age (r = -0.37, P = 0.2; r = -0.84, P = 0.002; and r = -0.6, P = 0.05). Despite this, insulin resistance increased, demonstrated by raised fasting insulin and fall in homeostasis model assessment insulin sensitivity with age (r = -0.64, P = 0.02). [[ALMS1]] mutations were identified in 10 of 12 patients, with a potential founder mutation in exon 16 present in five [np 10775del (C); Del3592fs/ter3597]. No genotype-phenotype correlation was observed. We identified mutations in [[ALMS1]] in more than 80% of patients with no genotype-phenotype correlation. In AS, severe childhood obesity, waist circumference, and body fat decrease with age, whereas insulin resistance increases. The abdominal obesity, insulin resistance, diabetes, hypertriglyceridemia, and hypertension suggest that AS could represent a monogenic model for the metabolic syndrome.
|mesh-terms=* Absorptiometry, Photon
* Adipose Tissue
* Adolescent
* Adult
* Aging
* Anthropometry
* Body Composition
* Body Mass Index
* Cell Cycle Proteins
* Child
* Child, Preschool
* DNA Mutational Analysis
* Diabetes Mellitus
* Female
* Founder Effect
* Genotype
* Hearing Loss, Sensorineural
* Humans
* Hyperinsulinism
* Hypertension
* Hypertriglyceridemia
* Insulin Resistance
* Male
* Mutation
* Obesity
* Phenotype
* Proteins
* Syndrome
* United Kingdom

|full-text-url=https://sci-hub.do/10.1210/jc.2005-2633
}}