A novel mutation of intron 22 in Janus kinase 3–deficient severe combined immunodeficiency

Severe combined immunodeficiency (SCID) comprises a heterogeneous group of inherited immunologic disorders with profound defects in cellular and humoral immunity. SCID is the most severe PID and constitutes a pediatric emergency. Affected children are highly susceptible to bacterial, viral, fungal, and opportunistic infections with life-threatening in the absence of hematopoietic stem cell transplantation. We report here two cases of SCID. The first case is a girl diagnosed with SCID at birth based on her family history and lymphocyte subpopulation typing. The second case is a 4-month-old boy with a history of recurrent opportunistic infections, BCGitis, and failure to thrive, and the immunology workup confirms a SCID phenotype. The genetic study in the two cases revealed a novel mutation in the RAG2 gene, c.826G > A (p.Gly276Ser), in a homozygous state. The novel mutation in the RAG2 gene identified in our study may help the early diagnosis of SCID.

Download Full-text

Cutaneous Granulomas with Predominantly CD8+ Lymphocytic Infiltrate in a Child with Severe Combined Immunodeficiency

Journal of Cutaneous Medicine and Surgery ◽

10.2310/7750.2008.07061 ◽

2008 ◽

Vol 12 (5) ◽

pp. 246-248 ◽

Cited By ~ 8

Author(s):

Stamatis Gregoriou ◽

Georgios Trimis ◽

Christina Charissi ◽

Dimitris Kalogeromitros ◽

Kalliopi Stefanaki ◽

...

Keyword(s):

Deoxyribonucleic Acid ◽

Dna Analysis ◽

Severe Combined Immunodeficiency ◽

Janus Kinase ◽

Lymphocytic Infiltrate ◽

Laboratory Evaluation ◽

Multiple Infections ◽

Combined Immunodeficiency ◽

Granulomatous Lesions ◽

History Of

Background: Combined immunodeficiency disorders comprise a heterogeneous group of diseases characterized by both humoral and cell-mediated immunodeficiency. Cutaneous granulomas manifestations in children with combined immunodeficiency are rare. Objective: We report the case of a 6-year-old boy who presented with disseminated cutaneous granulomas and a history of multiple infections. Methods and Results: Laboratory evaluation revealed severe combined immunodeficiency, and deoxyribonucleic acid (DNA) analysis confirmed mutations on a gene of chromosome 19 that encodes an enzyme called Janus kinase 3 (Jak-3). Immunohistochemistry revealed expression of CD8+ in the perivascular lymphocytic infiltrate Conclusion: Disseminated granulomatous lesions in children with a history of frequent infections should prompt the clinician to initiate detailed immunocompetence evaluation as they might prove to be the first manifestation of immunologic impairment.

Download Full-text

Mutation analyses and prenatal diagnosis in families of X-linked severe combined immunodeficiency caused by IL2Rγ gene novel mutation

Genetics and Molecular Research ◽

10.4238/2015.june.9.2 ◽

2015 ◽

Vol 14 (2) ◽

pp. 6164-6172 ◽

Cited By ~ 4

Author(s):

Q.L. Bai ◽

N. Liu ◽

X.D. Kong ◽

X.J. Xu ◽

Z.H. Zhao

Keyword(s):

Prenatal Diagnosis ◽

Novel Mutation ◽

Severe Combined Immunodeficiency ◽

Combined Immunodeficiency ◽

Mutation Analyses

Download Full-text

Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation

Blood ◽

10.1182/blood-2003-06-2104 ◽

2004 ◽

Vol 103 (6) ◽

pp. 2009-2018 ◽

Cited By ~ 88

Author(s):

Joseph L. Roberts ◽

Andrea Lengi ◽

Stephanie M. Brown ◽

Min Chen ◽

Yong-Jie Zhou ◽

...

Keyword(s):

Stem Cell ◽

T Cell ◽

Stem Cell Transplantation ◽

B Cell ◽

Cell Transplantation ◽

Severe Combined Immunodeficiency ◽

Interleukin 2 ◽

Janus Kinase ◽

Cell Functions ◽

Janus Kinase 3

Abstract We found 10 individuals from 7 unrelated families among 170 severe combined immunodeficiency (SCID) patients who exhibited 9 different Janus kinase 3 (JAK3) mutations. These included 3 missense and 2 nonsense mutations, 1 insertion, and 3 deletions. With the exception of 1 individual with persistence of transplacentally transferred maternal lymphocytes, all infants presented with a T–B+NK– phenotype. The patient mutations all resulted in abnormal B-cell Janus kinase 3 (JAK3)–dependent interleukin-2 (IL-2)–induced signal transducer and activator of transcription-5 (STAT5) phosphorylation. Additional analyses of mutations permitting protein expression revealed the N-terminal JH7 (del58A) and JH6 (D169E) domain mutations each inhibited receptor binding and catalytic activity, whereas the G589S JH2 mutation abrogated kinase activity but did not affect γc association. Nine of the 10 patients are currently alive from between 4 years and 18 years following stem cell transplantation, with all exhibiting normal T-cell function. Reconstitution of antibody function was noted in only 3 patients. Natural killer (NK) function was severely depressed at presentation in the 4 patients studied, whereas after transplantation the only individuals with normal NK lytic activity were patients 1 and 5. Hence, bone marrow transplantation is an effective means for reconstitution of T-cell immunity in this defect but is less successful for restoration of B-cell and NK cell functions.

Download Full-text