DOCK8-related Immunodeficiency Syndrome (DIDS): Report of Novel Mutations in Iranian Patients.
DIDS
DOCK8
HIES
Hyper IgE
Job syndrome
WES
Journal
Journal of molecular neuroscience : MN
ISSN: 1559-1166
Titre abrégé: J Mol Neurosci
Pays: United States
ID NLM: 9002991
Informations de publication
Date de publication:
Dec 2021
Dec 2021
Historique:
received:
23
03
2021
accepted:
12
04
2021
pubmed:
6
5
2021
medline:
3
3
2022
entrez:
5
5
2021
Statut:
ppublish
Résumé
DOCK8 immunodeficiency syndrome (DIDS) is a rare autosomal recessive (AR) disorder characterized by elevated serum IgE levels, eosinophilia, recurrent cutaneous infections, severe eczema, and sinopulmonary and gastrointestinal infections. This syndrome is a multisystem disease that is associated with both immune deficiency and neurological complications. In this study, we describe the clinical characteristics of two Iranian patients with DOCK8 deficiency and propose possible mechanisms for this condition. By using whole exome sequencing (WES), we identified two novel mutations, namely c.3233_3234del AG (p.Q1078fs) in exon 6 and a large deletion with 94 kb (c.405-3231 deletion, p.K135fs), in these two patients. These variations are confirmed with Sanger sequencing and CGH array. Subsequent co-segregation analysis is performed to identify inheritance patterns. Both patients were homozygote and their parents were heterozygote for the variations. For further investigation, prediction tools were applied to identify the pathogenicity of the variations and also for modeling the truncated proteins. The patients did not show neurological abnormalities associated with a deficiency of the N terminal region of DOCK8. The absence of neurological complications in the first patient is justifiable due to the maintenance of the proline-rich region in DOCK8, but for the second patient with expanded deletion which is almost like null DOCK8 protein, it is not presumable, pointing to the fact that the C terminal region of the protein might have functions in the proliferation and migration neurons in the peripheral nervous system. Alternatively, it is possible that neurological abnormalities follow an age-dependent pattern, leading to the appearance of related symptoms later in life. Further multiple functional studies are needed to model different identified variants in animal models to confirm our results and suggest possible mechanisms associated with DOCK8 deficiency in this study.
Identifiants
pubmed: 33948880
doi: 10.1007/s12031-021-01843-5
pii: 10.1007/s12031-021-01843-5
doi:
Substances chimiques
DOCK8 protein, human
0
Guanine Nucleotide Exchange Factors
0
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2456-2461Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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