A novel splice-site mutation in the common gamma chain (?c) geneIL2RG results in X-linked severe combined immunodeficiency with an atypical NK+ phenotype

2004 ◽  
Vol 23 (5) ◽  
pp. 522-523 ◽  
Author(s):  
Samantha L. Ginn ◽  
Christine Smyth ◽  
Melanie Wong ◽  
Bruce Bennetts ◽  
Peter B. Rowe ◽  
...  
Keyword(s):  
Splice Site ◽  
Severe Combined Immunodeficiency ◽  
Splice Site Mutation ◽  
Combined Immunodeficiency ◽  
Site Mutation ◽  
Gamma Chain ◽  
Common Gamma Chain ◽  
The Common

A Novel Splice Site Variant in FOXN1 in A Patient with Abnormal Newborn Screening for Severe Combined Immunodeficiency and Congenital Lymphopenia

2021 ◽  
Author(s):  
Ori Scott ◽  
Jenny Garkaby ◽  
Jessica Willett-Pachul ◽  
Yehonatan Pasternak
Keyword(s):  
Splice Site ◽  
Severe Combined Immunodeficiency ◽  
Splice Site Mutation ◽  
Missense Mutations ◽  
Combined Immunodeficiency ◽  
Site Mutation ◽  
Cd8 Cells ◽  
Cell Counts ◽  
Epithelial Development ◽  
Whole Exome

Background: The Forkhead box protein N1 (FOXN1) is a key regulator of thymic epithelial development, and its complete deficiency leads to a nude-severe combined immunodeficiency (SCID) phenotype. More recently, heterozygous mutations in FOXN1 have been linked with a syndrome of congenital lymphopenia and a wide clinical spectrum, with most cases being caused by missense mutations. Aim: To broaden the genotypic and phenotypic spectrum of heterozygous FOXN1 deficiency. Methods: Case report of a patient with FOXN1 haploinsufficiency due to a novel splice-site mutation. Results: Our patient was identified at 3 weeks of life given an abnormal newborn screen (NBS) for SCID, and was found to have congenital lymphopenia preferentially affecting CD8+ T-cells. Her cellular and humoral function were both excellent, and she has remained entirely asymptomatic and thriving for the first 3 years of her life. The patient was found on whole exome sequencing to carry a heterozygous splice-site mutation in the FOXN1 gene, affecting the Forkhead domain. The mutation was also identified in her asymptomatic mother. Conclusion: Heterozygous FOXN1 mutations are an increasingly-recognized cause of congenital lymphopenia. Our experience suggests most patients remain clinically well, with main manifestation including T-lymphopenia, mostly affecting CD8+ cells. Identification of the same variant in an asymptomatic parent suggests age-dependent improvement in T-cell counts and an overall benign course, while provides impetus for diligent conservative management with regular follow-up.

Detection of T lymphocytes with a second-site mutation in skin lesions of atypical X-linked severe combined immunodeficiency mimicking Omenn syndrome

Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 1872-1875 ◽  
Author(s):  
Taizo Wada ◽  
Masahiro Yasui ◽  
Tomoko Toma ◽  
Yuko Nakayama ◽  
Mika Nishida ◽  
...  
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Severe Combined Immunodeficiency ◽  
Phenotypic Expression ◽  
Splice Site Mutation ◽  
Skin Lesions ◽  
Omenn Syndrome ◽  
Combined Immunodeficiency ◽  
Site Mutation ◽  
Gamma Chain

Abstract X-linked severe combined immunodeficiency (XSCID) is caused by mutations of the common gamma chain (γc) and usually characterized by the absence of T and natural killer (NK) cells. Here, we report an atypical case of XSCID presenting with autologous T and NK cells and Omenn syndrome-like manifestations. The patient carried a splice-site mutation (IVS1+5G>A) that caused most of the mRNA to be incorrectly spliced but produced normally spliced transcript in lesser amount, leading to residual γc expression and development of T and NK cells. The skin biopsy specimen showed massive infiltration of revertant T cells. Those T cells were found to have a second-site mutation and result in complete restoration of correct splicing. These findings suggest that the clinical spectrum of XSCID is quite broad and includes atypical cases mimicking Omenn syndrome, and highlight the importance of revertant mosaicism as a possible cause for variable phenotypic expression.

Mutations in the gene for the common gamma chain (γc) in X-linked severe combined immunodeficiency

1998 ◽  
Vol 103 (6) ◽  
pp. 730-731 ◽  
Author(s):  
Sebastian D. Fugmann ◽  
Susanna Müller ◽  
Wilhelm Friedrich ◽  
Claus R. Bartram ◽  
K. Schwarz
Keyword(s):  
Severe Combined Immunodeficiency ◽  
Combined Immunodeficiency ◽  
Gamma Chain ◽  
Common Gamma Chain ◽  
The Common

Interleukin-2 receptor common gamma chain (IL2RG) defects present a diagnostic challenge

2018 ◽  
Vol 5 (4) ◽  
pp. 130-134
Author(s):  
Caroline Weisser ◽  
Dennis E. Bulman ◽  
Kayla Flamenbaum ◽  
Maian Roifman
Keyword(s):  
Genetic Analysis ◽  
Severe Combined Immunodeficiency ◽  
Genetic Defect ◽  
Interleukin 2 ◽  
Combined Immunodeficiency ◽  
Gamma Chain ◽  
Gene Encoding ◽  
Common Gamma Chain ◽  
Interleukin 2 Receptor ◽  
The Common

Background: The protein encoded by interleukin-2 receptor common gamma chain (IL2RG) is an important signaling component of many interleukin receptors, including those of interleukin-2, -4, -7, and -21, known as the common gamma chain. Mutations in the gene encoding the common gamma chain of the interleukin-2 receptor cause X-linked severe combined immunodeficiency (SCID). In this report, we present an unknown genetic defect of a patient diagnosed with SCID whose genetic analysis was performed 2 decades later. Methods: Whole genome sequencing and Sanger confirmation were used to identify a novel frameshift mutation in IL2RG. Massively parallel sequencing of genes associated with SCID were performed on the patient’s mother and sister. Results: Next generation sequencing techniques identified a heterozygous frame-shift deletion in the gene encoding the common gamma chain of IL2RG in our patient. The patient’s mother had a low level mosaicism for the same deletion. The sister had no detectable deletion. Conclusion: We have identified a novel mutation in IL2RG resulting in an X-linked SCID phenotype. The genetic analysis of the patient’s mother revealed a mosaicism which was not passed on to his sister. The importance of genetic analysis in family members and SCID patients with an unknown genetic defect should be emphasized for family planning and subsequent genetic counseling. Statement of novelty: Genetic testing is an extremely important component in evaluating severe combined immunodeficiency as it impacts treatment course and prognosis, and allows for genetic analysis and counselling of family members.

A synonymous splice site mutation in IL2RG gene causes late-onset combined immunodeficiency

2019 ◽  
Vol 109 (5) ◽  
pp. 603-611 ◽  
Author(s):  
Motoi Yamashita ◽  
Ryosuke Wakatsuki ◽  
Tamaki Kato ◽  
Tsubasa Okano ◽  
Shingo Yamanishi ◽  
...  
Keyword(s):  
Splice Site ◽  
Late Onset ◽  
Splice Site Mutation ◽  
Combined Immunodeficiency ◽  
Site Mutation ◽  
Il2rg Gene

Suspected Atypical Common Gamma Chain Severe Combined Immunodeficiency

2006 ◽  
Vol 117 (2) ◽  
pp. S288
Author(s):  
A. Chandra ◽  
D. Webster ◽  
K.C. Gilmour ◽  
D.S. Kumararatne ◽  
A. Thrasher
Keyword(s):  
Severe Combined Immunodeficiency ◽  
Combined Immunodeficiency ◽  
Gamma Chain ◽  
Common Gamma Chain

Homozygosity for the common GAA gene splice site mutation c.-32-13T>G in Pompe disease is associated with the classical adult phenotypical spectrum

2015 ◽  
Vol 25 (9) ◽  
pp. 719-724 ◽  
Author(s):  
Olimpia Musumeci ◽  
Andrea Thieme ◽  
Kristl G. Claeys ◽  
Stephan Wenninger ◽  
Rudolf A. Kley ◽  
...  
Keyword(s):  
Splice Site ◽  
Pompe Disease ◽  
Splice Site Mutation ◽  
Site Mutation ◽  
The Common ◽  
C 32 ◽  
Gaa Gene

scholarly journals Gene therapy improves immune function in preadolescents with X-linked severe combined immunodeficiency

Blood ◽  
2007 ◽  
Vol 110 (1) ◽  
pp. 67-73 ◽  
Author(s):  
Javier Chinen ◽  
Joie Davis ◽  
Suk See De Ravin ◽  
Beverly N. Hay ◽  
Amy P. Hsu ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Cell Function ◽  
Severe Combined Immunodeficiency ◽  
Marrow Transplant ◽  
Salvage Treatment ◽  
Combined Immunodeficiency ◽  
Gamma Chain ◽  
Gene Encoding ◽  
Il2rg Gene ◽  
The Common

Retroviral gene therapy can restore immunity to infants with X-linked severe combined immunodeficiency (XSCID) caused by mutations in the IL2RG gene encoding the common gamma chain (γc) of receptors for interleukins 2 (IL-2), −4, −7, −9, −15, and −21. We investigated the safety and efficacy of gene therapy as salvage treatment for older XSCID children with inadequate immune reconstitution despite prior bone marrow transplant from a parent. Subjects received retrovirus-transduced autologous peripherally mobilized CD34+ hematopoietic cells. T-cell function significantly improved in the youngest subject (age 10 years), and multilineage retroviral marking occurred in all 3 children.

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