title: Whole-exome sequencing identifies a novel ALMS1 mutation (p.Q2051X) in two Japanese brothers with Alström syndrome.
abstract: OBJECTIVE
  No mutations associated with Alström syndrome (AS), a rare autosomal recessive disease, have been reported in the Japanese population. The purpose of this study was to investigate the genetic and clinical features of two brothers with AS in a consanguineous Japanese family.
  
  
  METHODS
  Whole-exome sequencing analysis was performed on two brothers with AS and their unaffected parents. We performed a complete ophthalmic examination, including decimal best-corrected visual acuity, slit-lamp and funduscopic examination, visual-field and color-vision testing, full-field electroretinography, and optical coherence tomography. Fasting blood tests and systemic examinations were also performed.
  
  
  RESULTS
  A novel mutation (c.6151C>T in exon 8) in the Alström syndrome 1 (ALMS1) gene that causes a premature termination codon at amino acid 2051 (p.Q2051X), was identified in the homozygous state in the affected brothers and in the heterozygous state in the parents. The ophthalmologic findings for both brothers revealed infantile-onset severe retinal degeneration and visual impairment, marked macular thinning, and severe cataracts. Systemic findings showed hepatic dysfunction, hyperlipidemia, hypogonadism, short stature, and wide feet in both brothers, whereas hearing loss, renal failure, abnormal digits, history of developmental delay, scoliosis, hypertension, and alopecia were not observed in either brother. The older brother exhibited type 2 diabetic mellitus and obesity, whereas the younger brother had hyperinsulinemia and subclinical hypothyroidism.
  
  
  CONCLUSIONS
  A novel ALMS1 mutation was identified by using whole-exome sequencing analysis, which is useful not only to identify a disease causing mutation but also to exclude other gene mutations. Although characteristic ophthalmologic findings and most systemic findings were similar between the brothers, the brothers differed slightly in terms of glucose tolerance and thyroid function.
authors: Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan ; Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
authors: Satoshi
authors: S
authors: Katagiri
authors: Kazutoshi
authors: K
authors: Yoshitake
authors: Masakazu
authors: M
authors: Akahori
authors: Takaaki
authors: T
authors: Hayashi
authors: Masaaki
authors: M
authors: Furuno
authors: Jo
authors: J
authors: Nishino
authors: Kazuho
authors: K
authors: Ikeo
authors: Hiroshi
authors: H
authors: Tsuneoka
authors: Takeshi
authors: T
authors: Iwata
mesh_terms: D000328:Adult; D056769:Alstrom Syndrome / Q000208:ethnology / Q000235:genetics* / Q000473:pathology*; D044466:Asian People; D018797:Cell Cycle Proteins; D018389:Codon, Nonsense; D003241:Consanguinity; D059472:Exome; D005091:Exons; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D011506:Proteins / Q000235:genetics*; D017422:Sequence Analysis, DNA; D035781:Siblings
chemical_list: C490729:ALMS1 protein, human; D018797:Cell Cycle Proteins; D018389:Codon, Nonsense; D011506:Proteins