title: Molecular approach in the study of Alström syndrome: analysis of ten Spanish families.
abstract: OBJECTIVE
  To describe the clinical and genetic findings in 11 Spanish patients with confirmed (n=5) or suspected (n=6) Alström syndrome (AS).
  
  
  METHODS
  Patients underwent clinical evaluation, and were screened for variations in Alström syndrome 1 gene (ALMS1) using a genotyping microarray from Asper Ophthalmics and by direct sequencing of coding exons 8, 10, and 16 of ALMS1. Furthermore, we analyzed the presence of the A229T variant of retinitis pigmentosa GTPase regulator-interacting protein 1-like gene (RPGRIP1L) with direct sequencing of coding exon 6.
  
  
  RESULTS
  A great phenotypic variability was observed in our patients. Four mutations in ALMS1-two novel nonsense mutations in one family (p.Y1715X and p.S616X), one previously described mutation in homozygous state in another family (p.V3597Efs*4), and a likely pathogenic missense variation p.P1822L in a third family-were identified with direct sequencing. All patients were homozygous for 229A allele of RPGRIP1L, with the exception of a p.A229T heterozygous patient.
  
  
  CONCLUSIONS
  Our findings expand the spectrum of ALMS1 mutations causing Alström syndrome. The phenotypic differences between patients could be attributed to interactions with other genes inherited independently from the ALMS1 gene or with environmental factors. A clear understanding of the phenotypic spectrum in AS will be important to unravel the molecular mechanisms underlying this syndrome.
authors.affiliation: Departmento de Bioquímica, Genética e Inmunología, Facultad de Biología, Universidad de Vigo, Vigo, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Piñeiro-Gallego
authors.forename: Marta
authors.initials: M
authors.lastname: Cortón
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
authors.forename: Montserrat
authors.initials: M
authors.lastname: Baiget
authors.forename: Diana
authors.initials: D
authors.lastname: Valverde
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D056769:Alstrom Syndrome / Q000235:genetics*; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002648:Child; D005091:Exons; D005260:Female; D056726:Genetic Association Studies; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013030:Spain; D044465:White People / Q000235:genetics*
chemical_list: C490729:ALMS1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D011506:Proteins; C532826:RPGRIP1L protein, human