Renal Ciliopathies and Nephronophthisis

Gene: PDIA6

I don't know

Upgraded to Amber in view of the functional data.

Created: 14 Apr 2021, 10:18 a.m. | Last Modified: 14 Apr 2021, 10:18 a.m.

Panel Version: 0.140

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes

I don't know

2nd patient with large polycystic kidneys, death and end stage renal failure at 18 months, microcephaly, bilateral inguinal hernias, umbilical hernia, developmental delay, bilateral sensorineural hearing loss, visual impairment, steatorrhea, fibrotic changes in liver, and insulin-dependent diabetes. WGS found homozygous stop-gain variant (Tyr368*) in PDIA6. Segregation not performed.

Created: 17 Nov 2022, 12:57 a.m. | Last Modified: 17 Nov 2022, 12:57 a.m.

Panel Version: 1.13

1 case with asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes. Whole exome sequencing revealed a homozygous frameshift variant in the PDIA6 gene. RNA expression was reduced in a gene dosage‐dependent manner, supporting a loss‐of‐function effect of this variant. Phenotypic correlation with the previously reported mouse model recapitulated the growth defect and delay, early lethality, coagulation, diabetes, immunological, and polycystic kidney disease phenotypes. The phenotype of the current patient is consistent with phenotypes associated with the disruption of PDIA6 and the sensors of UPR in mice and humans.
Sources: Literature

Created: 14 Apr 2021, 6:07 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Polycystic kidney disease, infancy-onset diabetes, and microcephaly

Publications

• PMID: 35856135