Predominantly Antibody Deficiency

Gene: PIK3R1

Green List (high evidence)

Mono-allelic variants are also associated with SHORT syndrome.

Short syndrome: S = stature; H = hyperextensibility of joints or hernia (inguinal) or both; O = ocular depression; R = Rieger anomaly; T = teething delay. Also there is a recognisable facial gestalt (triangular facies, lack of facial fat, and hypoplastic nasal alae with overhanging columella), and near-universal partial lipodystrophy, insulin resistance, nephrocalcinosis, and hearing deficits. Both developmental milestones and cognition are normal for individuals with SHORT syndrome.

Thauvin-Robinet et al. (2013) reported 9 patients from 8 families with SHORT syndrome with heterozygous variants in PIK3R1. Further 2 families reported by Chudasama et al. (2013) and 3 families reported by Dyment et al. (2013). More cases reported in 2020-2021.

Created: 18 Aug 2021, 3:20 a.m. | Last Modified: 18 Aug 2021, 3:20 a.m.

Panel Version: 0.8855

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
SHORT syndrome, MIM # 269880

Publications

• 23810378
• 23810379
• 23810382

Green List (high evidence)

36 cases with PIK3R1-associated immunodeficiency were detected with c.1425+1G>A (42%), c.1425+1G>C (29%), c.1425+1G>T (13%). Four additional cases had mutations involving c.1425+2, and another had a G-C substitution at the -1 position of the splice acceptor site of exon 11. Analysis of patient mRNA demonstrated that all of the variants cause skipping of exon 11 (coding exon 10).
On the IUIS CVID phenotype gene list for human inborn errors of immunity (PMID: 32048120).
Sources: Expert list

Created: 21 Jul 2020, 4:25 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Immunodeficiency 36 MIM#616005

Publications

• 32048120
• 27076228