PIK3R1 Mutation Associated with Hyper IgM (APDS2 Syndrome): A Case Report and Review of the Literature.
APDS2
Activated phosphoinositide 3-kinase Delta Syndrome (APDS)
Hyper IgM syndrome
PASLI-R1
PIK3R1
Primary immunodeficiency
p85α.
Journal
Endocrine, metabolic & immune disorders drug targets
ISSN: 2212-3873
Titre abrégé: Endocr Metab Immune Disord Drug Targets
Pays: United Arab Emirates
ID NLM: 101269157
Informations de publication
Date de publication:
2019
2019
Historique:
received:
12
11
2018
revised:
08
01
2019
accepted:
07
02
2019
pubmed:
26
2
2019
medline:
31
3
2020
entrez:
26
2
2019
Statut:
ppublish
Résumé
APDS [Activated phosphoinositide 3-kinase (PI3K) δ Syndrome] is a newly found special form of primary immunodeficiency caused by mutations in genes encoding PI3Kδ subunits and over-activation of the PI3K signaling pathway. Gain-of-function and loss-of-function mutations in PIK3CD (encoding P110δ) and PIK3R1 (encoding p85α, p55α and p50α) lead to APDS1 and APDS2, respectively. The subsequent irregular PI3K downstream signaling cascade is associated with abnormalities in B cells and T cells and the consequent heterogeneous clinical manifestations including respiratory tract infections, autoimmunity, lymphoproliferation and not to mention primary antibody deficiency. In this study, we report a 12-year-old girl with a mutation in the PIK3R1 gene who manifested immunological phenotypes resembling hyper IgM syndrome along with a review of the literature of the previously reported patients. Whole exome sequencing was performed to detect the underlying genetic mutation in this patient. A de novo heterozygous splice site mutation in the hot spot of the PIK3R1 gene within the intron 10 was found (c.1425+1G>A). Further investigations are required for evaluation of the underlying genetic defects and the possible associations between genetic underpinning and heterogeneous severity and features of the disease.
Sections du résumé
BACKGROUND AND OBJECTIVE
OBJECTIVE
APDS [Activated phosphoinositide 3-kinase (PI3K) δ Syndrome] is a newly found special form of primary immunodeficiency caused by mutations in genes encoding PI3Kδ subunits and over-activation of the PI3K signaling pathway. Gain-of-function and loss-of-function mutations in PIK3CD (encoding P110δ) and PIK3R1 (encoding p85α, p55α and p50α) lead to APDS1 and APDS2, respectively. The subsequent irregular PI3K downstream signaling cascade is associated with abnormalities in B cells and T cells and the consequent heterogeneous clinical manifestations including respiratory tract infections, autoimmunity, lymphoproliferation and not to mention primary antibody deficiency. In this study, we report a 12-year-old girl with a mutation in the PIK3R1 gene who manifested immunological phenotypes resembling hyper IgM syndrome along with a review of the literature of the previously reported patients.
METHODS
METHODS
Whole exome sequencing was performed to detect the underlying genetic mutation in this patient.
RESULTS
RESULTS
A de novo heterozygous splice site mutation in the hot spot of the PIK3R1 gene within the intron 10 was found (c.1425+1G>A).
CONCLUSION
CONCLUSIONS
Further investigations are required for evaluation of the underlying genetic defects and the possible associations between genetic underpinning and heterogeneous severity and features of the disease.
Identifiants
pubmed: 30799802
pii: EMIDDT-EPUB-96842
doi: 10.2174/1871530319666190225114739
doi:
Substances chimiques
PIK3R1 protein, human
EC 2.7.1.-
Class I Phosphatidylinositol 3-Kinases
EC 2.7.1.137
Class Ia Phosphatidylinositol 3-Kinase
EC 2.7.1.137
Types de publication
Case Reports
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
941-958Informations de copyright
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