Cilia, Alström syndrome--molecular mechanisms and therapeutic perspectives.
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.
Mihai
Cristina Maria
CM
Department of Pediatrics, "Ovidius" University, Faculty of Medicine, 124 Mamaia Blvd., 900527 Constanta, Romania. cristinamaria_mihai@hotmail.com
Catrinoiu
Doina
D
Marshall
Jan
J
Stoicescu
Ramona
R
Tofolean
Ioan Tiberiu
IT
D000015:Abnormalities, Multiple / Q000235:genetics; D000328:Adult; D056769:Alstrom Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D001766:Blindness / Q000235:genetics; D015992:Body Mass Index; D018797:Cell Cycle Proteins; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002923:Cilia / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D034381:Hearing Loss / Q000235:genetics; D019382:Human Growth Hormone / Q000627:therapeutic use; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D009154:Mutation; D009765:Obesity / Q000235:genetics; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics; D016896:Treatment Outcome
C490729:ALMS1 protein, human; D018797:Cell Cycle Proteins; D005819:Genetic Markers; D011506:Proteins; D019382:Human Growth Hormone