https://nova.newcastle.edu.au/vital/access/ /manager/Index en-au 5 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:54895 Wed 20 Mar 2024 13:33:17 AEDT ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49050 Wed 03 May 2023 15:40:01 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:55161 Tue 16 Apr 2024 15:43:27 AEST ]]> https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38947 MTPAP/TENT6, encoding mitochondrial poly(A) polymerase (MTPAP), was first reported in six individuals of Old Order Amish descent demonstrating an early-onset, progressive spastic ataxia with optic atrophy and learning difficulties. MTPAP contributes to the regulation of mitochondrial gene expression through the polyadenylation of mitochondrially encoded mRNAs. Mitochondrial mRNAs with severely truncated poly(A) tails were observed in affected individuals, and mitochondrial protein expression was altered. Objective: To determine the genetic basis of a perinatal encephalopathy associated with stereotyped neuroimaging and infantile death in three patients from two unrelated families. Methods: Whole-exome sequencing was performed in two unrelated patients and the unaffected parents of one of these individuals. Variants and familial segregation were confirmed by Sanger sequencing. Polyadenylation of mitochondrial transcripts and de novo synthesis of mitochondrial proteins were assessed in patient's fibroblasts. Results: Compound heterozygous p.Ile428Thr and p.Arg523Trp substitutions in MTPAP were recorded in two affected siblings from one family, and a homozygous p.Ile385Phe missense variant identified in a further affected child from a second sibship. Mitochondrial poly(A) tail analysis demonstrated shorter posttranscriptional additions to the mitochondrial transcripts, as well as an altered expression of mitochondrial proteins in the fibroblasts of the two siblings compared with healthy controls. Conclusion: Mutations in MTPAP likely cause an autosomal recessive perinatal encephalopathy with lethality in the first year of life.]]> Fri 11 Mar 2022 12:45:18 AEDT ]]>