2016
DOI: 10.1016/j.clim.2016.09.011
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Gain-of-function mutation in PIK3R1 in a patient with a narrow clinical phenotype of respiratory infections

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Cited by 19 publications
(7 citation statements)
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“…6,7 The nomenclature APDS2 started being used to discriminate these patients from those carrying mutations in PIK3CD. Although almost all patients with APDS2 reported to date have exon-skipping mutations resulting in a central deletion of amino acid residues 434 to 475 of p85a, 6,7,11,[21][22][23][24][25][26][27] more recently, a heterozygous missense mutation in the iSH2 domain of PIK3R1 has been shown to cause APDS2. 20 These LOF PIK3R1 mutations disrupt interaction of the 2 subunits and lead to a loss of inhibition of the catalytic subunit p110d by p85, therefore behaving as PI3Kd GOF mutations.…”
Section: Immunodeficiency Caused By Overactivation Of the Pi3kd Pathwmentioning
confidence: 99%
“…6,7 The nomenclature APDS2 started being used to discriminate these patients from those carrying mutations in PIK3CD. Although almost all patients with APDS2 reported to date have exon-skipping mutations resulting in a central deletion of amino acid residues 434 to 475 of p85a, 6,7,11,[21][22][23][24][25][26][27] more recently, a heterozygous missense mutation in the iSH2 domain of PIK3R1 has been shown to cause APDS2. 20 These LOF PIK3R1 mutations disrupt interaction of the 2 subunits and lead to a loss of inhibition of the catalytic subunit p110d by p85, therefore behaving as PI3Kd GOF mutations.…”
Section: Immunodeficiency Caused By Overactivation Of the Pi3kd Pathwmentioning
confidence: 99%
“…While a few isolated cases have been identified who are completely asymptomatic ( 20 ) or who have severe extrapulmonary manifestations but minimal or no respiratory symptomatology ( 21 ), recurrent respiratory tract infections are reported near universally in APDS; indeed, they may be the sole manifestation of the disease ( 16 ), and they may be both very frequent and severe ( 5 ). Unfortunately, however, differences in definitions and nomenclature make direct comparisons between published studies challenging at times.…”
Section: Respiratory Infections In Apdsmentioning
confidence: 99%
“…Improvements in sinopulmonary infection have been reported following hematopoietic stem cell transplantation, with the majority of surviving patients no longer requiring immunoglobulin therapy ( 50 ); however, this procedure carries a significant mortality and will not alleviate established structural lung damage such as bronchiectasis. Early identification of patients with APDS ( 16 ) may allow transplantation before the development of such complications; however, the clinical heterogeneity makes prediction of future disease severity challenging.…”
Section: Management Of the Respiratory Manifestations Of Apdsmentioning
confidence: 99%
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“…Clinically, these mutations can lead to varied phenotypes, and original PIK3CD cohorts were identified by screening patients with recurrent chest infections ( 114 ) and herpesviral infections ( 65 ), respectively. Patients with activating mutations in PIK3R1 leading to an increased PI3Kδ activity also have primary immunodeficiency ( 67 , 69 , 116 123 ), and many studies, including large cohort studies, have defined new mutations in PIK3CD leading to activated PI3K delta syndrome (APDS) and expanded the phenotype of disease ( 64 , 66 , 67 , 124 131 ). While the clinical features of patients with mutations in PIK3CD and PIK3R1 can be similar, there is evidence that PIK3R1 mutations can also have extra-immune phenotypes ( 118 ).…”
Section: Introductionmentioning
confidence: 99%