Expanding the Nude SCID/CID Phenotype Associated with FOXN1 Homozygous, Compound Heterozygous, or Heterozygous Mutations
| Autor: | Muge Sayitoglu, Raif S. Geha, Luca Maragliano, Carla Borzacchiello, A Worth, Ghassan Dbaibo, Moaffaq Mahdi, Bénédicte Neven, Peter Ciznar, Ioanna A. Rota, Ana E. Sousa, José Gonçalo Marques, Akella Radha Rama Devi, Emilia Cirillo, Rima Hanna-Wakim, E. Graham Davies, Giuliana Giardino, Alexandra Y. Kreins, Janet Chou, Sule Haskologlu, Georg A. Holländer, Fabio Benfenati, Candan Islamoglu, Figen Dogu, Fatima Dhalla, Claudio Pignata, Sinem Firtina, Aydan Ikinciogullari, Svetlana O. Sharapova |
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| Přispěvatelé: | Repositório da Universidade de Lisboa, İstinye Üniversitesi, Mühendislik ve Doğa Bilimleri Fakültesi, Moleküler Biyoloji ve Genetik Bölümü, Sinem Fırtına / 0000-0002-3370-8545, Fırtına, Sinem, Sinem Fırtına / X-8520-2018, Sinem Fırtına / 16642650000, Giardino, G., Sharapova, S. O., Ciznar, P., Dhalla, F., Maragliano, L., Radha Rama Devi, A., Islamoglu, C., Ikinciogullari, A., Haskologlu, S., Dogu, F., Hanna-Wakim, R., Dbaibo, G., Chou, J., Cirillo, E., Borzacchiello, C., Kreins, A. Y., Worth, A., Rota, I. A., Marques, J. G., Sayitoglu, M., Firtina, S., Mahdi, M., Geha, R., Neven, B., Sousa, A. E., Benfenati, F., Hollander, G. A., Davies, E. G., Pignata, C. |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
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 |
| Zdroj: | Journal of Clinical Immunology Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| ISSN: | 1573-2592 0271-9142 |
| Popis: | © 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/. 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. |
| Databáze: | OpenAIRE |
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