Abstract
Mutations in the Janus Kinase 3 (JAK3) gene cause an autosomal recessive form of severe combined immunodeficiency (SCID) usually characterized by the absence of both T and NK cells, but preserved numbers of B lymphocytes (T-B+NK-SCID). The detection of larger (>100 bp) genomic duplications or deletions can be more difficult to be detected by PCR-based methods or standard NGS protocols, and a broad range of mutation detection techniques are necessary. We report four unrelated Italian patients (two females and two males) with SCID phenotype. Protein expression, functional studies, molecular analysis by standard methods and NGS, and transcripts studies were performed to obtain a definitive diagnosis. Here, we describe four JAK3-deficient patients from four unrelated families. The first patient is homozygous for the known c.1951 C>T mutation causing the amino acidic change p.R651W. The other two patients, originating from the same small Italian town, resulted compound heterozygotes for the same g.15410_16542del deletion and two different novel mutations, g.13319_13321delTTC and c.933T>G (p.F292V), respectively. The fourth patient was compound heterozygous for the novel mutations p.V599G and p.W709R. Defective STAT5 phosphorylation ...Continue Reading
References
Jun 25, 1999·Molecular Genetics and Metabolism·P L Deininger, M A Batzer
Jan 11, 2000·Molecular and Cellular Biology·M ChenJ J O'Shea
Nov 4, 2000·The New England Journal of Medicine·R H Buckley
Jun 1, 2001·Human Mutation·W Xiao, P J Oefner
Oct 23, 2001·Human Mutation·L D NotarangeloR F Schumacher
Jan 10, 2002·Genes and Immunity·D M FruchtF Candotti
Nov 15, 2003·Blood·Joseph L RobertsRebecca H Buckley
Jun 29, 2004·Molecular Immunology·John J O'SheaFabio Candotti
Jan 13, 2005·The Journal of Pediatrics·Ilhan TezcanGenevieve De Saint Basile
Sep 30, 2005·Pediatrics International : Official Journal of the Japan Pediatric Society·Toru UchiyamaShigeru Tsuchiya
Apr 17, 2007·The Journal of Allergy and Clinical Immunology·Christopher M MjaanesErwin W Gelfand
Feb 11, 2009·The Journal of Allergy and Clinical Immunology·Denise WalsheKimberly C Gilmour
Jun 23, 2009·Nature Reviews. Immunology·Yrina RochmanWarren J Leonard
Dec 25, 2010·Journal of Clinical Immunology·Pamela P W LeeYu-Lung Lau
Sep 3, 2011·Pediatric Transplantation·Grace P YuMorton J Cowan
Dec 2, 2011·Acta Biochimica Et Biophysica Sinica·Wei Wu, Xiao-Hong Sun
Dec 6, 2011·The Pediatric Infectious Disease Journal·Zobaida AlsumSaleh Al-Muhsen
Dec 30, 2011·Genome Biology·Prescott Deininger
Jul 25, 2014·The Biochemical Journal·Jeffrey J BabonLeila N Varghese
Aug 19, 2014·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·F TosatoM Plebani
Nov 8, 2015·The Journal of Allergy and Clinical Immunology·Alessia ScarselliCaterina Cancrini
Jan 16, 2016·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Polina StepenskyYaacov Barak
Sep 18, 2017·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Farah QamarRaif S Geha
Citations
Feb 19, 2020·Genome Medicine·Jacob J AdashekRazelle Kurzrock
Dec 20, 2018·Immunological Reviews·Leen MoensIsabelle Meyts
Aug 29, 2019·Frontiers in Immunology·Emilia CirilloClaudio Pignata
Apr 30, 2019·Frontiers in Immunology·Cristina CifaldiGigliola Di Matteo
Oct 12, 2020·Clinical and Experimental Immunology·R El HawaryA Elmarsafy
Jan 23, 2021·Autoimmunity Reviews·Elvira FavoinoFederico Perosa