Prevalent Pathogenic Variants of ATP7B in Chinese Patients with Wilson's Disease: Geographical Distribution and Founder Effect.
Genes (Basel)
; 12(3)2021 02 25.
Article
en En
| MEDLINE
| ID: mdl-33668890
ABSTRACT
Wilson's disease (WD) is an autosomal recessive disorder caused by ATP7B pathogenic variants. This study aimed to show the geographical distribution and haplotype spectrum of three prevalent pathogenic variants (p.R778L, p.P992L, p.T935M) in mainland Chinese population and clarify whether the founder effect may account for their origins. We firstly summarized the frequency and geographical distribution of p.R778L, p.P992L and p.T935M in 715 WD patients. Then, to construct haplotypes associated with the three variants, Sanger sequencing and microsatellite typing at three dinucleotide-repeat markers (D13S314, D13S301, D13S316) flanking the ATP7B gene were performed in 102 WD families. An obvious regional-specific distribution feature was found in p.T935M. Linkage disequilibrium at the three markers was shown in all the three variants and we found the common haplotypes specific for p.R778L, p.P992L and p.T935M respectively, represented successively by 10-7-7, 10-9-5 and 12-4-8, which all exhibited great significance vs. the control chromosomes (p < 0.01). Meanwhile, haplotypes for the three variants differed from the studies in other regions to some extent. The common haplotypes we found indicate that three prevalent pathogenic variants emerge due to the founder effect. Furthermore, the study contributes to expand our knowledge of the genetic diversity of WD from a cross-regional perspective.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Análisis de Secuencia de ADN
/
Sustitución de Aminoácidos
/
Pueblo Asiatico
/
ATPasas Transportadoras de Cobre
/
Degeneración Hepatolenticular
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Humans
País/Región como asunto:
Asia
Idioma:
En
Revista:
Genes (Basel)
Año:
2021
Tipo del documento:
Article
País de afiliación:
China