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APDS2 and SHORT Syndrome in a Teenager with PIK3R1 Pathogenic Variant.

Authors
  • Ramirez, Lourdes1
  • Tamayo, Wendy2
  • Ale, Hanadys3
  • 1 Department of Pediatrics, Joe DiMaggio Children's Hospital, 1005 Joe DiMaggio Dr, Hollywood, FL, 33021, USA. [email protected]
  • 2 Department of Medicine, Herbert Wertheim College of Medicine, 11200 SW 8th St, Miami, FL, 33199, USA.
  • 3 Department of Pediatric Allergy and Immunology, Joe DiMaggio Children's Hospital, 1005 Joe DiMaggio Dr, Hollywood, FL, 33021, USA.
Type
Published Article
Journal
Journal of Clinical Immunology
Publisher
Springer-Verlag
Publication Date
Aug 10, 2020
Identifiers
DOI: 10.1007/s10875-020-00843-1
PMID: 32778990
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Activated PI3K δ syndrome (APDS) is a primary immunodeficiency caused by heterogeneous germline gain-of-function mutations which ultimately lead to the hyperactivation of the phosphoinositide-3-kinase δ (PI3K δ). PI3K δ exists as a heterodimer composed of a catalytic and a regulatory subunit. APDS type 2 is caused by mutations in the PIK3R1 gene affecting the p85α regulatory subunit. SHORT syndrome is a rare multisystem disorder characterized by short stature, hyperextensible joints, ocular depression, Rieger anomaly, and tooth eruption delay. The primary causes of SHORT syndrome are heterozygous loss-of-function mutations in the PIK3R1 gene. The combination of APDS2 and SHORT syndrome is rare, with few cases reported to date. Here we describe a 17-year-old female with phenotypic features consistent with SHORT syndrome and history of sinopulmonary infections and hypogammaglobulinemia. Invitae immunodeficiency panel genetic testing revealed a pathogenic loss-of-function variant in an intronic splice site in the gene PIK3R1 (c.1425 + 1G > C). This pathogenic variant had been previously associated with APDS2; however, it had not been associated with SHORT syndrome. The exact mechanisms linking both conditions are yet to be identified. This case report emphasizes the importance of screening for comorbidities associated with SHORT syndrome in APDS2 patients and vice versa.

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