Dataset Information

Cilia, Alstrom syndrome--molecular mechanisms and therapeutic perspectives.

ABSTRACT: Over the past ten years, several studies demonstrated the connections between cilia, basal bodies and human diseases with a wide phenotypic spectrum, including randomization of body symmetry, obesity, cystic kidney diseases and retinal degeneration. Alström syndrome (OMIM 203800) first described in 1959, is a rare autosomal recessive disorder caused by mutations in a novel gene of unknown function, ALMS1, located on the short arm of chromosome 2. Central features of Alström syndrome include obesity, insulin resistance, and type 2 diabetes. About 500 individuals with Alström syndrome are known worldwide. ALMS1 is widely expressed and localizes to centrosomes and to the base of cilia. We discuss the possible molecular mechanisms, clinical features, and future therapeutic options in a patient diagnosed with this rare disease. Monogenic defects causing human obesity actually disrupt hypothalamic pathways with a profound effect on satiety and food intake. A potential contributor to obesity- cilia with impaired function or abnormal structure, creates a new link to be studied in the future, between these organelles and the genetics of obesity.

SUBMITTER: Mihai CM

PROVIDER: S-EPMC5654309 | biostudies-literature | 2008 Jul-Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cilia, Alström syndrome--molecular mechanisms and therapeutic perspectives.

Mihai Cristina Maria CM Catrinoiu Doina D Marshall Jan J Stoicescu Ramona R Tofolean Ioan Tiberiu IT

Journal of medicine and life 20080701 3

Over the past ten years, several studies demonstrated the connections between cilia, basal bodies and human diseases with a wide phenotypic spectrum, including randomization of body symmetry, obesity, cystic kidney diseases and retinal degeneration. Alström syndrome (OMIM 203800) first described in 1959, is a rare autosomal recessive disorder caused by mutations in a novel gene of unknown function, ALMS1, located on the short arm of chromosome 2. Central features of Alström syndrome include obes ...[more]

PMID: 20108502

Similar Datasets

Project description:Alström syndrome (ALMS) is an autosomal recessive disease characterized by multiple organ involvement, including neurosensory vision and hearing loss, childhood obesity, diabetes mellitus, cardiomyopathy, hypogonadism, and pulmonary, hepatic, renal failure and systemic fibrosis. Alström Syndrome is caused by mutations in ALMS1, and ALMS1 protein is thought to have a role in microtubule organization, intraflagellar transport, endosome recycling and cell cycle regulation. Here, we report extensive phenotypic and genetic analysis of a large cohort of Turkish patients with ALMS. We evaluated 61 Turkish patients, including 11 previously reported, for both clinical spectrum and mutations in ALMS1. To reveal the molecular diagnosis of the patients, different approaches were used in combination, a cohort of patients were screened by the gene array to detect the common mutations in ALMS1 gene, then in patients having any of the common ALMS1 mutations were subjected to direct DNA sequencing or next-generation sequencing for the screening of mutations in all coding regions of the gene. In total, 20 distinct disease-causing nucleotide changes in ALMS1 have been identified, eight of which are novel, thereby increasing the reported ALMS1 mutations by 6% (8/120). Five disease-causing variants were identified in more than one kindred, but most of the alleles were unique to each single patient and identified only once (16/20). So far, 16 mutations identified were specific to the Turkish population, and four have also been reported in other ethnicities. In addition, 49 variants of uncertain pathogenicity were noted, and four of these were very rare and probably or likely deleterious according to in silico mutation prediction analyses. ALMS has a relatively high incidence in Turkey and the present study shows that the ALMS1 mutations are largely heterogeneous; thus, these data from a particular population may provide a unique source for the identification of additional mutations underlying Alström Syndrome and contribute to genotype-phenotype correlation studies.

Dataset Information

Cilia, Alstrom syndrome--molecular mechanisms and therapeutic perspectives.

Publications

Cilia, Alström syndrome--molecular mechanisms and therapeutic perspectives.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets