Phenotypic and mutational spectrum of 21 Chinese patients with Alström syndrome

Am J Med Genet A. 2020 Feb;182(2):279-288. doi: 10.1002/ajmg.a.61412. Epub 2019 Nov 22.


Alström syndrome (AS) is a monogenic syndromic ciliopathy caused by mutations in the ALMS1 (Alström Syndrome 1) gene. A total of 21 subjects with AS from 20 unrelated Chinese families were recruited. Our cohort consists of 9 females and 12 males, between 5 months and 20 years old. The first symptom(s) appeared between 3 and 24 months. They were recorded to be either visual impairments (83%) or dilated cardiomyopathy (17%). Median time from symptom onset to seeking medical attention was 6 months (3-36 months) and the median time needed to reach the final molecular diagnosis is 54 months (6-240 months). System involvement at the time of the survey was as follows: visual symptoms (100%), hearing Impairment (67%), endocrine symptoms (43%), neurological symptoms (19%), hepatic symptoms (14%), and renal Involvement (14%). These findings are comparable to data reported in the literature. However, the proportion of subjects with cognitive impairment (33%) and behavioral problems (19%) were higher. Thirty-three unique mutations were identified in the ALMS1 gene, of which 18 are novel mutations classified as pathogenic/likely pathogenic according to the American College of Medical Genetics (ACMG) guideline. Four recurrent mutations were identified in the cohort, in particular; c.2084C>A, p. (Ser695Ter), is suggestive to be a founder mutation in people of Chinese ancestry. The participation of AS subjects of differing ethnicities is essential to improve the algorithm in facial recognition/phenotyping, as well as to understand the mutation spectrum beyond than just those of European ancestry.

Keywords: ALMS1; Alstrom syndrome; Chinese.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Alstrom Syndrome / genetics*
  • Alstrom Syndrome / pathology
  • Cell Cycle Proteins / genetics*
  • Child
  • Child, Preschool
  • DNA Mutational Analysis / methods
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Infant
  • Male
  • Mutation / genetics*
  • Pedigree
  • Young Adult


  • ALMS1 protein, human
  • Cell Cycle Proteins