Lipodystrophy - childhood onset
Gene: PCNT
Comment on list classification: There is sufficient evidence available for promoting this gene to green rating at the next GMS review.Created: 6 Aug 2023, 6:13 p.m. | Last Modified: 6 Aug 2023, 6:13 p.m.
Panel Version: 4.18
Of 21 patients with biallelic PCNT variants, 18 had insulin resistance, which was severe in the majority of patients. Ten patients had confirmed diabetes (mean age of onset 15 years), and 13 had metabolic dyslipidemia. All patients without insulin resistance were younger than 4 years old. In addition, knockdown of PCNT in adipocytes had no effect on proximal insulin signaling but produced a two-fold impairment in insulin-stimulated glucose uptake, approximately commensurate with an associated defect in cell proliferation and adipogenesis (PMID:21270239).Created: 6 Aug 2023, 6:10 p.m. | Last Modified: 6 Aug 2023, 6:10 p.m.
Panel Version: 4.15
This gene was added on recommendation of NHSE Genomic Medicine Service:
Severe insulin resistance in the absence of frank lipodystrophy is a common feature of Microcephalic osteodysplastic primordial dwarfism, type II due to PCNT mutations (PMID: 21270239). Along with ALMS1 and POC1A it is part of a cluster of genes that cause severe insulin resistance syndromes and affect the centrosome/primary cillium though the precise mechanistic basis for the impairment in insulin action is unclear.Created: 2 Aug 2023, 11:35 a.m. | Last Modified: 3 Aug 2023, 6:39 p.m.
Panel Version: 4.15
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Microcephalic osteodysplastic primordial dwarfism, type II, Severe insulin resistance
Publications
Gene: pcnt has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: PCNT were changed from Microcephalic osteodysplastic primordial dwarfism, type II, Severe insulin resistance to Microcephalic osteodysplastic primordial dwarfism, type II, OMIM:210720; Insulin resistance, HP:0000855
Publications for gene: PCNT were set to
Tag Q3_23_promote_green tag was added to gene: PCNT. Tag Q3_23_NHS_review tag was added to gene: PCNT.
gene: PCNT was added gene: PCNT was added to Lipodystrophy - childhood onset. Sources: Expert list,NHS GMS Mode of inheritance for gene: PCNT was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PCNT were set to Microcephalic osteodysplastic primordial dwarfism, type II, Severe insulin resistance