Expanding the genetic spectrum of the pyruvate carboxylase deficiency with novel missense, deep intronic and structural variants.
| Title: | Expanding the genetic spectrum of the pyruvate carboxylase deficiency with novel missense, deep intronic and structural variants. |
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| Authors: | Tsygankova P; Research centre for medical genetics, Moscow, Russia, Moskvoreche, 1, 15552 Moscow, Russia.; Bychkov I; Research centre for medical genetics, Moscow, Russia, Moskvoreche, 1, 15552 Moscow, Russia.; Minzhenkova M; Research centre for medical genetics, Moscow, Russia, Moskvoreche, 1, 15552 Moscow, Russia.; Pechatnikova N; Morozov Children's City Clinical Hospital, 4th Dobryninskij per, 1/9, Moscow, Russia.; Bessonova L; Research centre for medical genetics, Moscow, Russia, Moskvoreche, 1, 15552 Moscow, Russia.; Buyanova G; Regional Children's Clinical Hospital of Chelyabinsk, 454076 Chelyabinsk, 42a Blucher Street, Russia.; Naumchik I; Republican scientific medical center 'Mother and child', Minsk, Belarus, 66 Orlovskaya str., Minsk 220053, Belarus.; Beskorovainiy N; Research centre for medical genetics, Moscow, Russia, Moskvoreche, 1, 15552 Moscow, Russia.; Tabakov V; Research centre for medical genetics, Moscow, Russia, Moskvoreche, 1, 15552 Moscow, Russia.; Itkis Y; Research centre for medical genetics, Moscow, Russia, Moskvoreche, 1, 15552 Moscow, Russia.; Shilova N; Research centre for medical genetics, Moscow, Russia, Moskvoreche, 1, 15552 Moscow, Russia.; Zakharova E; Research centre for medical genetics, Moscow, Russia, Moskvoreche, 1, 15552 Moscow, Russia. |
| Source: | Molecular genetics and metabolism reports [Mol Genet Metab Rep] 2022 Jun 23; Vol. 32, pp. 100889. Date of Electronic Publication: 2022 Jun 23 (Print Publication: 2022). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Inc Country of Publication: United States NLM ID: 101624422 Publication Model: eCollection Cited Medium: Print ISSN: 2214-4269 (Print) Linking ISSN: 22144269 NLM ISO Abbreviation: Mol Genet Metab Rep Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: [New York, NY] : Elsevier Inc., [2014]- |
| Abstract: | Introduction: Pathogenic variants in the pyruvate carboxylase (PC) gene cause a wide spectrum of recessive phenotypes, ranging from the early-onset fatal encephalopathy to the adult-onset benign form.; Results: Patient 1 is a 6 y.o. boy with ataxia, hypoglycemia and episodes of lactic acidosis. WGS revealed the novel heterozygous missense variant c.1372A > G (p.Asn458Asp) in the PC gene. Additional analysis revealed discordant reads mapped to chromosomes 11 and 1, so a reciprocal translocation disrupted the PC gene was suspected. The translocation was validated via FISH-analysis and Sanger sequencing of its boundaries.Patient 2 is a 13 y.o. girl with psychomotor delay, episodes of lactic acidosis and ketonuria. WES revealed the novel homozygous intronic variant c.1983-116C > T. The PC's mRNA analysis demonstrated the exonization of several intron 16 sequences and some residual amount of WT mRNA isoform.Two other patients had more severe course of the disease. Their genotype represents missense variants in compound heterozygous and homozygous state (c.1876C > T (p.Arg626Trp), c.2606G > C (p.Gly869Ala), c.2435C > A (p.Ala812Asp).; Conclusion: In patients with metabolic crises, lactic acidosis and hypoglycemia analysis of PC gene is recommended. WGS with deep bioinformatic analysis should be taken into consideration when none or the only one pathogenic variant in the PC gene is found.; (© 2022 The Authors.) |
| Competing Interests: | All authors have seen and approved the manuscript. All authors declare no conflict of interest. |
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| Contributed Indexing: | Keywords: Deep intronic variants; Pyruvate carboxylase deficiency; Reciprocal translocations; WES; WGS |
| Entry Date(s): | Date Created: 20220705 Latest Revision: 20220716 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC9240867 |
| DOI: | 10.1016/j.ymgmr.2022.100889 |
| PMID: | 35782291 |
| Database: | MEDLINE |
Journal Article