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Expanding the Nude SCID/CID Phenotype Associated with FOXN1 Homozygous, Compound Heterozygous, or Heterozygous Mutations
- Source :
- Journal of Clinical Immunology, Repositório Científico de Acesso Aberto de Portugal, Repositório Científico de Acesso Aberto de Portugal (RCAAP), instacron:RCAAP
- Publication Year :
- 2021
- Publisher :
- Springer US, 2021.
-
Abstract
- © The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.<br />Human nude SCID is a rare autosomal recessive inborn error of immunity (IEI) characterized by congenital athymia, alopecia, and nail dystrophy. Few cases have been reported to date. However, the recent introduction of newborn screening for IEIs and high-throughput sequencing has led to the identification of novel and atypical cases. Moreover, immunological alterations have been recently described in patients carrying heterozygous mutations. The aim of this paper is to describe the extended phenotype associated with FOXN1 homozygous, compound heterozygous, or heterozygous mutations. We collected clinical and laboratory information of a cohort of 11 homozygous, 2 compound heterozygous, and 5 heterozygous patients with recurrent severe infections. All, except one heterozygous patient, had signs of CID or SCID. Nail dystrophy and alopecia, that represent the hallmarks of the syndrome, were not always present, while almost 50% of the patients developed Omenn syndrome. One patient with hypomorphic compound heterozygous mutations had a late-onset atypical phenotype. A SCID-like phenotype was observed in 4 heterozygous patients coming from the same family. A spectrum of clinical manifestations may be associated with different mutations. The severity of the clinical phenotype likely depends on the amount of residual activity of the gene product, as previously observed for other SCID-related genes. The severity of the manifestations in this heterozygous family may suggest a mechanism of negative dominance of the specific mutation or the presence of additional mutations in noncoding regions.
- Subjects :
- 0301 basic medicine
Male
Models, Molecular
FOXN1
DNA Mutational Analysis
Molecular Conformation
Compound heterozygosity
0302 clinical medicine
Immunology and Allergy
heterozygous
Homozygous
Dominance (genetics)
nail dystrophy
Homozygote
Hematopoietic Stem Cell Transplantation
Disease Management
High-Throughput Nucleotide Sequencing
Forkhead Transcription Factors
heterozygou
Phenotype
Pedigree
Treatment Outcome
Child, Preschool
Original Article
Female
Omenn syndrome
Heterozygote
Immunology
homozygous
Cell Line
Gene product
03 medical and health sciences
Structure-Activity Relationship
Nude SCID
medicine
Compound heterozygous
Humans
Nail dystrophy
Genetic Predisposition to Disease
Gene
Genetic Association Studies
compound heterozygous
Newborn screening
business.industry
compound heterozygou
Alopecia
medicine.disease
alopecia
030104 developmental biology
Heterozygous
Genetic Loci
Mutation
Severe Combined Immunodeficiency
business
EBV-related lymphoproliferative disease
homozygou
030215 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 15732592 and 02719142
- Volume :
- 41
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Journal of Clinical Immunology
- Accession number :
- edsair.doi.dedup.....71f93e2f8920d101e5992eb97d15e3b0