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Primary immunodeficiency diseases : Genomic approaches delineate heterogeneous Mendelian disorders

Stray-Pedersen, Asbjorg (author)
Sorte, Hanne Sormo (author)
Samarakoon, Pubudu (author)
show more...
Gambin, Tomasz (author)
Chinn, Ivan K. (author)
Akdemir, Zeynep H. Coban (author)
Erichsen, Hans Christian (author)
Forbes, Lisa R. (author)
Gu, Shen (author)
Yuan, Bo (author)
Jhangiani, Shalini N. (author)
Muzny, Donna M. (author)
Rodningen, Olaug Kristin (author)
Sheng, Ying (author)
Nicholas, Sarah K. (author)
Noroski, Lenora M. (author)
Seeborg, Filiz O. (author)
Davis, Carla M. (author)
Canter, Debra L. (author)
Mace, Emily M. (author)
Vece, Timothy J. (author)
Allen, Carl E. (author)
Abhyankar, Harshal A. (author)
Boone, Philip M. (author)
Beck, Christine R. (author)
Wiszniewski, Wojciech (author)
Fevang, Borre (author)
Aukrust, Pal (author)
Tjonnfjord, Geir E. (author)
Gedde-Dahl, Tobias (author)
Hjorth-Hansen, Henrik (author)
Dybedal, Ingunn (author)
Nordoy, Ingvild (author)
Jorgensen, Silje F. (author)
Abrahamsen, Tore G. (author)
Overland, Torstein (author)
Bechensteen, Anne Grete (author)
Skogen, Vegard (author)
Osnes, Liv T. N. (author)
Kulseth, Mari Ann (author)
Prescott, Trine E. (author)
Rustad, Cecilie F. (author)
Heimdal, Ketil R. (author)
Belmont, John W. (author)
Rider, Nicholas L. (author)
Chinen, Javier (author)
Cao, Tram N. (author)
Smith, Eric A. (author)
Soledad Caldirola, Maria (author)
Bezrodnik, Liliana (author)
Lugo Reyes, Saul Oswaldo (author)
Espinosa Rosales, Francisco J. (author)
Guerrero-Cursaru, Nina Denisse (author)
Pedroza, Luis Alberto (author)
Poli, Cecilia M. (author)
Franco, Jose L. (author)
Trujillo Vargas, Claudia M. (author)
Aldave Becerra, Juan Carlos (author)
Wright, Nicola (author)
Issekutz, Thomas B. (author)
Issekutz, Andrew C. (author)
Abbott, Jordan (author)
Caldwell, Jason W. (author)
Bayer, Diana K. (author)
Chan, Alice Y. (author)
Aiuti, Alessandro (author)
Cancrini, Caterina (author)
Holmberg, Eva (author)
West, Christina (author)
Umeå universitet,Pediatrik
Burstedt, Magnus (author)
Karaca, Ender (author)
Yesil, Gozde (author)
Artac, Hasibe (author)
Bayram, Yavuz (author)
Atik, Mehmed Musa (author)
Eldomery, Mohammad K. (author)
Ehlayel, Mohammad S. (author)
Jolles, Stephen (author)
Flato, Berit (author)
Bertuch, Alison A. (author)
Hanson, I. Celine (author)
Zhang, Victor W. (author)
Wong, Lee-Jun (author)
Hu, Jianhong (author)
Walkiewicz, Magdalena (author)
Yang, Yaping (author)
Eng, Christine M. (author)
Boerwinkle, Eric (author)
Gibbs, Richard A. (author)
Shearer, William T. (author)
Lyle, Robert (author)
Orange, Jordan S. (author)
Lupski, James R. (author)
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 (creator_code:org_t)
MOSBY-ELSEVIER, 2017
2017
English.
In: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 139:1, s. 232-245
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Background: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective: We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. Methods: Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results: A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/ 110) and management was directly altered in nearly a quarter (26/ 110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion: This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Keyword

Primary immunodeficiency disease
whole-exome sequencing
copy number variants

Publication and Content Type

ref (subject category)
art (subject category)

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Stray-Pedersen, ...
Sorte, Hanne Sor ...
Samarakoon, Pubu ...
Gambin, Tomasz
Chinn, Ivan K.
Akdemir, Zeynep ...
show more...
Erichsen, Hans C ...
Forbes, Lisa R.
Gu, Shen
Yuan, Bo
Jhangiani, Shali ...
Muzny, Donna M.
Rodningen, Olaug ...
Sheng, Ying
Nicholas, Sarah ...
Noroski, Lenora ...
Seeborg, Filiz O ...
Davis, Carla M.
Canter, Debra L.
Mace, Emily M.
Vece, Timothy J.
Allen, Carl E.
Abhyankar, Harsh ...
Boone, Philip M.
Beck, Christine ...
Wiszniewski, Woj ...
Fevang, Borre
Aukrust, Pal
Tjonnfjord, Geir ...
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Hjorth-Hansen, H ...
Dybedal, Ingunn
Nordoy, Ingvild
Jorgensen, Silje ...
Abrahamsen, Tore ...
Overland, Torste ...
Bechensteen, Ann ...
Skogen, Vegard
Osnes, Liv T. N.
Kulseth, Mari An ...
Prescott, Trine ...
Rustad, Cecilie ...
Heimdal, Ketil R ...
Belmont, John W.
Rider, Nicholas ...
Chinen, Javier
Cao, Tram N.
Smith, Eric A.
Soledad Caldirol ...
Bezrodnik, Lilia ...
Lugo Reyes, Saul ...
Espinosa Rosales ...
Guerrero-Cursaru ...
Pedroza, Luis Al ...
Poli, Cecilia M.
Franco, Jose L.
Trujillo Vargas, ...
Aldave Becerra, ...
Wright, Nicola
Issekutz, Thomas ...
Issekutz, Andrew ...
Abbott, Jordan
Caldwell, Jason ...
Bayer, Diana K.
Chan, Alice Y.
Aiuti, Alessandr ...
Cancrini, Cateri ...
Holmberg, Eva
West, Christina
Burstedt, Magnus
Karaca, Ender
Yesil, Gozde
Artac, Hasibe
Bayram, Yavuz
Atik, Mehmed Mus ...
Eldomery, Mohamm ...
Ehlayel, Mohamma ...
Jolles, Stephen
Flato, Berit
Bertuch, Alison ...
Hanson, I. Celin ...
Zhang, Victor W.
Wong, Lee-Jun
Hu, Jianhong
Walkiewicz, Magd ...
Yang, Yaping
Eng, Christine M ...
Boerwinkle, Eric
Gibbs, Richard A ...
Shearer, William ...
Lyle, Robert
Orange, Jordan S ...
Lupski, James R.
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MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Basic Medicine
and Medical Genetics
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Journal of Aller ...
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Umeå University

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