Phenotypic and mutational spectrum of 21 Chinese patients with Alström syndrome.
Am J Med Genet A
; 182(2): 279-288, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31755649
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ciclo Celular
/
Predisposição Genética para Doença
/
Síndrome de Alstrom
/
Mutação
Tipo de estudo:
Guideline
/
Prognostic_studies
/
Qualitative_research
Limite:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Revista:
Am J Med Genet A
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China