Whole exome sequencing in childhood-onset lupus frequently detects single gene etiologies.
Adolescent
Amino Acid Transport System y+L
/ genetics
Child
Child, Preschool
Complement C1q
/ genetics
Female
Gain of Function Mutation
/ genetics
Genetic Predisposition to Disease
/ genetics
Humans
Lupus Erythematosus, Systemic
/ genetics
Male
Mutation
/ genetics
PTEN Phosphohydrolase
/ genetics
STAT1 Transcription Factor
/ genetics
Exome Sequencing
/ methods
alpha-Mannosidase
/ genetics
Monogenic
SLE
WES
Journal
Pediatric rheumatology online journal
ISSN: 1546-0096
Titre abrégé: Pediatr Rheumatol Online J
Pays: England
ID NLM: 101248897
Informations de publication
Date de publication:
30 Jul 2019
30 Jul 2019
Historique:
received:
09
06
2019
accepted:
08
07
2019
entrez:
1
8
2019
pubmed:
1
8
2019
medline:
11
2
2020
Statut:
epublish
Résumé
Systemic lupus erythematosus (SLE) comprise a diverse range of clinical manifestations. To date, more than 30 single gene causes of lupus/lupus like syndromes in humans have been identified. In the clinical setting, identifying the underlying molecular diagnosis is challenging due to phenotypic and genetic heterogeneity. We employed whole exome sequencing (WES) in patients presenting with childhood-onset lupus with severe and/or atypical presentations to identify cases that are explained by a single-gene (monogenic) cause. From January 2015 to June 2018 15 new cases of childhood-onset SLE were diagnosed in Edmond and Lily Safra Children's Hospital. By WES we identified causative mutations in four subjects in five different genes: C1QC, SLC7A7, MAN2B1, PTEN and STAT1. No molecular diagnoses were established on clinical grounds prior to genetic testing. We identified a significant fraction of monogenic SLE etiologies using WES and confirm the genetic locus heterogeneity in childhood-onset lupus. These results highlight the importance of establishing a genetic diagnosis for children with severe or atypical lupus by providing accurate and early etiology-based diagnoses and improving subsequent clinical management.
Sections du résumé
BACKGROUND
BACKGROUND
Systemic lupus erythematosus (SLE) comprise a diverse range of clinical manifestations. To date, more than 30 single gene causes of lupus/lupus like syndromes in humans have been identified. In the clinical setting, identifying the underlying molecular diagnosis is challenging due to phenotypic and genetic heterogeneity.
METHODS
METHODS
We employed whole exome sequencing (WES) in patients presenting with childhood-onset lupus with severe and/or atypical presentations to identify cases that are explained by a single-gene (monogenic) cause.
RESULTS
RESULTS
From January 2015 to June 2018 15 new cases of childhood-onset SLE were diagnosed in Edmond and Lily Safra Children's Hospital. By WES we identified causative mutations in four subjects in five different genes: C1QC, SLC7A7, MAN2B1, PTEN and STAT1. No molecular diagnoses were established on clinical grounds prior to genetic testing.
CONCLUSIONS
CONCLUSIONS
We identified a significant fraction of monogenic SLE etiologies using WES and confirm the genetic locus heterogeneity in childhood-onset lupus. These results highlight the importance of establishing a genetic diagnosis for children with severe or atypical lupus by providing accurate and early etiology-based diagnoses and improving subsequent clinical management.
Identifiants
pubmed: 31362757
doi: 10.1186/s12969-019-0349-y
pii: 10.1186/s12969-019-0349-y
pmc: PMC6668194
doi:
Substances chimiques
Amino Acid Transport System y+L
0
SLC7A7 protein, human
0
STAT1 Transcription Factor
0
STAT1 protein, human
0
Complement C1q
80295-33-6
PTEN Phosphohydrolase
EC 3.1.3.67
PTEN protein, human
EC 3.1.3.67
alpha-Mannosidase
EC 3.2.1.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
52Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK076683
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK007726
Pays : United States
Organisme : Foundation for the National Institutes of Health
ID : T32DK-007726
Organisme : Foundation for the National Institutes of Health
ID : DK-076683-13
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