The diagnosis of PGK deficiency was made based on the remarkably low (<5% of normal) erythrocyte PGK enzyme activity level and the identification of a missense (c. 491A --> T) PGK1 gene mutation.
We studied two brothers with typical occipital horn syndrome and used yeast complementation and timed growth assays, exploiting a Saccharomyces cerevisiae mutant strain, to assess in vitro N1304S copper transport.
These findings identify G1019D as the first conditional mutation associated with Menkes disease and demonstrate correction of the mislocalized protein by copper supplementation.
An inosine monophosphate dehydrogenase 1 (IMPDH1) pseudogene carries a c.676G>A mutation that produces a p.Asp226Asn substitution that causes the retinitis pigmentosa 10 (RP10) form of adRP; and a phosphoglycerate kinase 1 (PGK1) pseudogene (PGK1P1) carries a c.837T>C mutation that produces a p.Ile252Thr substitution that is associated with a phosphoglycerate kinase deficiency.
Western blotting, in vitro expression analyses, immunohistochemistry, and yeast complementation assays using cultured fibroblasts from a classic Menkes disease patient all indicated small amounts of native ATP7A(R201X) read-through and were associated with a dramatic clinical response to early copper treatment.
To elucidate the molecular consequences of the ATP7A mutations, various mutations in ATP7A associated with distinct phenotypes of MD (L873R, C1000R, N1304S, and A1362D) were analyzed in detail.
We have generated an Atp7a conditional knock in mouse model of dHMNX expressing Atp7a(T985I), the orthologue of the human ATP7A(T994I) identified in dHMNX patients.
We previously identified two rare ATP7A missense mutations (P1386S and T994I) leading to a non-fatal form of motor neuron disorder, X-linked distal hereditary motor neuropathy (dHMNX), without overt signs of systemic Cu deficiency.
Phosphoglycerate kinase (PGK) activity was markedly decreased in muscle, and molecular analysis of the PGK1 gene identified the p.T378P mutation that was recently reported in a patient with isolated myopathy.
Variants highly perturbed in both catalytic efficiency (p.G158V, p.D164V, p.K191del, D285V, p.D315N, and p.T378P) and heat stability (all, but p.T378P) result to be mainly associated with myopathy alone.
An inosine monophosphate dehydrogenase 1 (IMPDH1) pseudogene carries a c.676G>A mutation that produces a p.Asp226Asn substitution that causes the retinitis pigmentosa 10 (RP10) form of adRP; and a phosphoglycerate kinase 1 (PGK1) pseudogene (PGK1P1) carries a c.837T>C mutation that produces a p.Ile252Thr substitution that is associated with a phosphoglycerate kinase deficiency.
An inosine monophosphate dehydrogenase 1 (IMPDH1) pseudogene carries a c.676G>A mutation that produces a p.Asp226Asn substitution that causes the retinitis pigmentosa 10 (RP10) form of adRP; and a phosphoglycerate kinase 1 (PGK1) pseudogene (PGK1P1) carries a c.837T>C mutation that produces a p.Ile252Thr substitution that is associated with a phosphoglycerate kinase deficiency.
An inosine monophosphate dehydrogenase 1 (IMPDH1) pseudogene carries a c.676G>A mutation that produces a p.Asp226Asn substitution that causes the retinitis pigmentosa 10 (RP10) form of adRP; and a phosphoglycerate kinase 1 (PGK1) pseudogene (PGK1P1) carries a c.837T>C mutation that produces a p.Ile252Thr substitution that is associated with a phosphoglycerate kinase deficiency.
The diagnosis of PGK deficiency was made based on the remarkably low (<5% of normal) erythrocyte PGK enzyme activity level and the identification of a missense (c. 491A --> T) PGK1 gene mutation.
To investigate the nigrostriatal system using 99mTc-TRODAT-1 SPECT binding and report the phenotype of three affected males with early onset levodopa responsive Parkinsonism harbouring the c.491 A > T/p.D164V pathogenic variant.
Immunoprecipitation assays revealed abnormal interaction between ATP7A(T994I) and p97/VCP, a protein mutated in two autosomal dominant forms of motor neuron disease.
Immunoprecipitation assays revealed an abnormal interaction between ATP7A(T994I) and p97/VCP, an ubiquitin-selective chaperone which is mutated in two autosomal dominant forms of motor neuron disease: amyotrophic lateral sclerosis and inclusion body myopathy with early-onset Paget disease and fronto-temporal dementia.
Immunoprecipitation assays revealed an abnormal interaction between ATP7A(T994I) and p97/VCP, an ubiquitin-selective chaperone which is mutated in two autosomal dominant forms of motor neuron disease: amyotrophic lateral sclerosis and inclusion body myopathy with early-onset Paget disease and fronto-temporal dementia.