title: Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alström syndrome.
abstract: Alström syndrome is a homogeneous autosomal recessive disorder that is characterized by childhood obesity associated with hyperinsulinemia, chronic hyperglycemia and neurosensory deficits. The gene involved in Alström syndrome probably interacts with genetic modifiers, as subsets of affected individuals present with additional features such as dilated cardiomyopathy, hepatic dysfunction, hypothyroidism, male hypogonadism, short stature and mild to moderate developmental delay, and with secondary complications normally associated with type 2 diabetes, such as hyperlipidemia and atherosclerosis. Our detection of an uncharacterized transcript, KIAA0328, led us to identify the gene ALMS1, which contains sequence variations, including four frameshift mutations and two nonsense mutations, that segregate with Alström syndrome in six unrelated families. ALMS1 is ubiquitously expressed at low levels and does not share significant sequence homology with other genes reported so far. The identification of ALMS1 provides an entry point into a new pathway leading toward the understanding of both Alström syndrome and the common diseases that characterize it.
authors.affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.
authors.forename: Gayle B
authors.initials: GB
authors.lastname: Collin
authors.forename: Jan D
authors.initials: JD
authors.lastname: Marshall
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ikeda
authors.forename: W Venus
authors.initials: WV
authors.lastname: So
authors.forename: Isabelle
authors.initials: I
authors.lastname: Russell-Eggitt
authors.forename: Pietro
authors.initials: P
authors.lastname: Maffei
authors.forename: Sebastian
authors.initials: S
authors.lastname: Beck
authors.forename: Cornelius F
authors.initials: CF
authors.lastname: Boerkoel
authors.forename: Nicola
authors.initials: N
authors.lastname: Sicolo
authors.forename: Mitchell
authors.initials: M
authors.lastname: Martin
authors.forename: Patsy M
authors.initials: PM
authors.lastname: Nishina
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Naggert
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002648:Child; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009410:Nerve Degeneration / Q000235:genetics*; D009490:Neurosecretory Systems / Q000473:pathology* / Q000503:physiopathology*; D009765:Obesity / Q000235:genetics*; D010375:Pedigree; D017386:Sequence Homology, Amino Acid; D013577:Syndrome
chemical_list: C510001:Alms1 protein, mouse; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004247:DNA