Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: RGS10

I don't know

3 patients (three brothers) from 1 non-consanguineous family in Qatar, compound heterozygous NM_001005339.2:c.489_491del (p.Glu163del, maternal) and c.511G>T (p.Ala171Ser, paternal). Combined immunodeficiency (polyclonal hypergammaglobulinemia, impaired polysaccharide response, poor NK cytotoxicity) plus growth hormone deficiency. Mechanism is multimorphic (mislocalization), not loss-of-function both variants retain full GAP activity but disrupt PKA-dependent nuclear relocalization. CRISPR-Cas9 correction restores chemotaxis specifically for RGS10 alleles, dissociated from a co-inherited PIK3CD/APDS variant present in all 3 patients. Note: maternal allele (p.Glu163del) is not rare in gnomAD (AF ~1.3x10^-3, ~30 homozygotes) disclosed, does not undermine the compound-heterozygous recessive model since disease requires combination with the near-private paternal allele. PMID 34315806.

Created: 6 Oct 2026, 6:07 p.m. | Last Modified: 6 Oct 2026, 6:07 p.m.

Panel Version: 9.109

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 34315806

Comment on list classification: New gene added by Boaz Palterer. Single family with 3 affected sibs reported (PMID:34315806), who presented with short stature and immunodeficiency and harboured compound het variants in RGS10 that segregated with disease. However, the sibs also carried a heterozygous PIK3CD (E525K) variant that has previously been deemed pathogenic in Activated PI3 Kinase Delta Syndrome (APDS), a primary immunodeficiency. The variant was excluded as the father also carried the PIK3CD variant but was mostly healthy and none of the 3 affected sibs displayed the full spectrum of symptoms associated with APDS. Nonetheless, APDS is a clinically heterogeneous condition with variable penetrance among affected individuals and so the contribution of PIK3CD to the patients immune dysregulation cannot be completely ruled out.

There are no further reports of an association between RGS10 variants and immunodeficiency to date, and therefore rating Red until further evidence emerges.

Created: 10 Aug 2021, 10:06 a.m. | Last Modified: 10 Aug 2021, 10:06 a.m.

Panel Version: 2.454

I don't know

Chinn et al. a kindred with three affected siblings presenting with short stature and immunodeficiency and segregating with biallelic variants in RGS10 (c.489_491del:p.E163del and c.G511T:p.A171S). The affected individuals exhibited systemic abnormalities directly related to the RGS10 mutations, including recurrent infections, hypergammaglobulinemia, profoundly reduced lymphocyte chemotaxis, abnormal lymph node architecture, and short stature due to growth hormone deficiency. Some functional data is presented.
Sources: Literature

Created: 30 Jul 2021, 8:21 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
short stature; GH deficiency; immunodeficiency; hypergammaglobulinemia; reduced lymphocyte chemotaxis

Publications

• 34315806