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| Skeletal ciliopathies v1.15 | PDIA6 | Eleanor Williams Classified gene: PDIA6 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v1.15 | PDIA6 | Eleanor Williams Added comment: Comment on list classification: Promoted from grey to amber. 1 case plus functional data. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v1.15 | PDIA6 | Eleanor Williams Gene: pdia6 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v1.14 | PDIA6 |
Eleanor Williams changed review comment from: Not associated with a phenotype in OMIM. In Gene2Phenotype it is associated with PDIA6-associated syndromic neonatal diabetes and asphyxiating thoracic dystrophy with Limited confidence. As Zornitza Stark reports PMID: 33495992 (Al-Fadhli et al 2021) describes one case of a child with asphyxiating thoracic dystrophy (ATD) syndrome and infantile-onset diabetes who had a homozygous frameshift variant in the PDIA6 gene (NM_001282704.1:c.703del (p.Val235fs)) which is in exon 8 (of 15). The parents and unaffected sibling were heterozygous for this variant. The authors state that PDIA6 is not known yet to be involved in the formation or function of the primary cilia but suggest that it could be directly or indirectly interacting or required for proper protein folding of known or unknown ciliopathy protein. The X-ray findings at 6 months were consistent with typical radiological features of ATD syndrome.; to: Not associated with a phenotype in OMIM. In Gene2Phenotype it is associated with PDIA6-associated syndromic neonatal diabetes and asphyxiating thoracic dystrophy with Limited confidence. As Zornitza Stark reports PMID: 33495992 (Al-Fadhli et al 2021) describes one case of a child with asphyxiating thoracic dystrophy (ATD) syndrome and infantile-onset diabetes who had a homozygous frameshift variant in the PDIA6 gene (NM_001282704.1:c.703del (p.Val235fs)) which is in exon 8 (of 15). The parents and unaffected sibling were heterozygous for this variant. The authors state that PDIA6 is not known yet to be involved in the formation or function of the primary cilia but suggest that it could be directly or indirectly interacting or required for proper protein folding of known or unknown ciliopathy protein. The X-ray findings at 6 months were consistent with typical radiological features of ATD syndrome. Other features include intrauterine growth retardation, multiple cysts in both kidneys associated with renal oligohydramnios (in first antenatal ultrasound) and hyperglycemia on the second day of life. |
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| Skeletal ciliopathies v1.14 | PDIA6 | Eleanor Williams commented on gene: PDIA6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Skeletal ciliopathies v1.10 | PDIA6 |
Zornitza Stark gene: PDIA6 was added gene: PDIA6 was added to Skeletal ciliopathies. Sources: Literature Mode of inheritance for gene: PDIA6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDIA6 were set to 33495992 Phenotypes for gene: PDIA6 were set to Asphyxiating thoracic dystrophy (ATD) syndrome and infantile‐onset diabetes Review for gene: PDIA6 was set to AMBER Added comment: 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. Rated Amber in view of the high impact variant combined with functional data including a mouse model. Sources: Literature |
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