Identification of FAT3 as a new candidate gene for adolescent idiopathic scoliosis.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
19 07 2022
19 07 2022
Historique:
received:
15
02
2022
accepted:
12
07
2022
entrez:
19
7
2022
pubmed:
20
7
2022
medline:
22
7
2022
Statut:
epublish
Résumé
In an effort to identify rare alleles associated with adolescent idiopathic scoliosis (AIS) whole-exome sequencing was performed on a discovery cohort of 73 unrelated patients and 70 age-and sex matched controls, all of French-Canadian ancestry. A collapsing gene burden test was performed to analyze rare protein-altering variants using case-control statistics. Since no single gene achieved statistical significance, targeted exon sequencing was performed for 24 genes with the smallest p values, in an independent replication cohort of unrelated severely affected females with AIS and sex-matched controls (N = 96 each). An excess of rare, potentially protein-altering variants was noted in one particular gene, FAT3, although it did not achieve statistical significance. Independently, we sequenced the exomes of all members of a rare multiplex family of three affected sisters and unaffected parents. All three sisters were compound heterozygous for two rare protein-altering variants in FAT3. The parents were single heterozygotes for each variant. The two variants in the family were also present in our discovery cohort. A second validation step was done, using another independent replication cohort of 258 unrelated AIS patients having reach their skeletal maturity and 143 healthy controls to genotype nine FAT3 gene variants, including the two variants previously identified in the multiplex family: p.L517S (rs139595720) and p.L4544F (rs187159256). Interestingly, two FAT3 variants, rs139595720 (genotype A/G) and rs80293525 (genotype C/T), were enriched in severe scoliosis cases (4.5% and 2.7% respectively) compared to milder cases (1.4% and 0.7%) and healthy controls (1.6% and 0.8%). Our results implicate FAT3 as a new candidate gene in the etiology of AIS.
Identifiants
pubmed: 35853984
doi: 10.1038/s41598-022-16620-6
pii: 10.1038/s41598-022-16620-6
pmc: PMC9296578
doi:
Substances chimiques
Cadherins
0
FAT3 protein, human
0
Epidermal Growth Factor
62229-50-9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12298Informations de copyright
© 2022. The Author(s).
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