A novel essential splice site variant in SPTB in a large hereditary spherocytosis family.
Mol Genet Genomic Med
; 9(5): e1641, 2021 05.
Article
in En
| MEDLINE
| ID: mdl-33943044
ABSTRACT
BACKGROUND:
We studied a large family with 22 individuals affected with autosomal dominant hereditary spherocytosis (HS).METHODS:
Genome-wide linkage, whole-genome sequencing (WGS), Sanger sequencing, RT-PCR, and ToPO TA cloning analyses were performed.RESULTS:
We revealed a heterozygous G>A transition in the 14q23 locus, at position +1 of the intron 8 donor splice site of the spectrin beta, erythrocytic (SPTB) gene. This splice variant (SPTB c.1064+1G>A) was confirmed by Sanger sequencing and showed complete co-segregation with HS in the family. Further RT-PCR reactions and sequencing analysis indicated that the variant leads to the exclusion of exon 8 and subsequent frameshift in exon 9 and a premature stop codon in SPTB. Translation of the altered allele would lead to a truncation with a loss of all spectrin repeat domains in SPTB protein.CONCLUSION:
This variant is novel and has not been found in any databases. We propose that this splice variant explains the spherocytosis phenotype observed in this large family.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Spherocytosis, Hereditary
/
Spectrin
/
RNA Splice Sites
Type of study:
Diagnostic_studies
Limits:
Adolescent
/
Adult
/
Child
/
Female
/
Humans
/
Male
Language:
En
Journal:
Mol Genet Genomic Med
Year:
2021
Document type:
Article
Affiliation country:
Estados Unidos