bims-meglyc Biomed News
on Metabolic disorders affecting glycosylation
Issue of 2023–03–05
fiveteen papers selected by
Silvia Radenkovic, Frontiers in Congenital Disorders of Glycosylation Consortium
  1. Policy for rare diseases.
  2. Diagnostics for rare diseases.
  3. Government launches action plan to improve care for people with rare diseases.
  4. Individualized ASO therapy for rare diseases.
  5. [Advances in the diagnosis and treatment of phosphomannomutase 2 deficiency].
  6. ALG11-CDG: novel variant and review of the literature.
  7. Gene-targeted therapies: Overview and implications.
  8. Genetics of neurological and psychiatric disorders.
  9. [A case of Congenital disorder of glycosylation due to SSR4 gene deletion].
  10. Patient engagement and involvement in rare disease research.
  11. TRAPPC2L-related disorder: first homozygous protein-truncating variant and further delineation of the phenotype.
  12. Towards a New Classification of Cardiomyopathies.
  13. Impact of Genetic Disorders in the Surgical Management of Congenital Heart Disease.
  14. New advances in CRISPR/Cas-mediated precise gene-editing techniques.
  15. Ethical principles for the usage and sharing of genomic data from researc.
  1. Commun Med (Lond). 2023 Feb 28. 3(1): 26
    Policy for rare diseases.
      
    DOI:  https://doi.org/10.1038/s43856-023-00254-4
  2. Commun Med (Lond). 2023 Feb 28. 3(1): 18
    Diagnostics for rare diseases.
      
    DOI:  https://doi.org/10.1038/s43856-023-00247-3
  3. BMJ. 2023 Feb 28. 380 p483
    Government launches action plan to improve care for people with rare diseases.
    Jacqui Wise.
      
    DOI:  https://doi.org/10.1136/bmj.p483
  4. Commun Med (Lond). 2023 Feb 28. 3(1): 27
    Individualized ASO therapy for rare diseases.
      
    DOI:  https://doi.org/10.1038/s43856-023-00255-3
  5. Zhongguo Dang Dai Er Ke Za Zhi. 2023 Feb 15. pii: 1008-8830(2023)02-0223-06. [Epub ahead of print]25(2): 223-228
    [Advances in the diagnosis and treatment of phosphomannomutase 2 deficiency].
    Shu-Yan Zhou.
      Phosphomannomutase 2 deficiency is the most common form of N-glycosylation disorders and is also known as phosphomannomutase 2-congenital disorder of glycosylation (PMM2-CDG). It is an autosomal recessive disease with multi-system involvements and is caused by mutations in the PMM2 gene (OMIM: 601785), with varying severities in individuals. At present, there is still no specific therapy for PMM2-CDG, and early identification, early diagnosis, and early treatment can effectively prolong the life span of pediatric patients. This article reviews the advances in the diagnosis and treatment of PMM2-CDG.
    Keywords:  Congenital disorder of glycosylation; Gene mutation; PMM2 gene; Phosphomannomutase 2 deficiency
    DOI:  https://doi.org/10.7499/j.issn.1008-8830.2209049
  6. J Pediatr Endocrinol Metab. 2023 Feb 28.
    ALG11-CDG: novel variant and review of the literature.
    Ayşenur Engin Erdal, Ahmet Cevdet Ceylan, Kıvılcım Gücüyener, Rıdvan Murat Öktem, Oya Kıreker Köylü, Çiğdem Seher Kasapkara.
       OBJECTIVES: Asparagine-dependent glycosylation 11-congenital disorders of glycosylation (ALG11-CDG) is a rare autosomal recessive N-glycosylation defect with multisystem involvement particularly neurological symptoms such as epilepsy and neuromotor developmental delay.
    CASE PRESENTATION: A 31-month-old male patient admitted to our center with complaints of axial hypotonia, drug-resistant myoclonic seizures, microcephaly and deafness. The electroencephalography (EEG) showed a burst-suppression pattern without hypsarrhythmia. Basal metabolic investigations were unremarkable. Progressive cerebral atrophy, hypomyelination and corpus callosum hypoplasia were striking features in brain MRI images taken during our follow-up. Compound heterozygous mutations of the ALG11 gene were found by whole exome sequencing (WES) analysis. It was determined that the c.476T>C mutation is a novel mutation. CDG type 1 pattern was detected with the examination of carbohydrate-deficient transferrin (CDT) by capillary zone electrophoresis.
    CONCLUSIONS: In patients with a possible congenital defect of glycosylation, a screening test such as CDT analysis is suggested. To discover novel mutations in this rare disease group, expanded genetic analysis should be performed.
    Keywords:  ALG11-CDG; carbohydrate-deficient transferrin; epileptic encephalopathy
    DOI:  https://doi.org/10.1515/jpem-2022-0480
  7. Am J Med Genet C Semin Med Genet. 2023 Mar 02.
    Gene-targeted therapies: Overview and implications.
    P J Brooks, Tiina K Urv, Melissa A Parisi.
      Gene-targeted therapies (GTTs) are therapeutic platforms that are in principle applicable to large numbers of monogenic diseases. The rapid development and implementation of GTTs have profound implications for rare monogenic disease therapy development. This article provides a brief summary of the primary types of GTTs and a brief overview of the current state of the science. It also serves as a primer for the articles in this special issue.
    DOI:  https://doi.org/10.1002/ajmg.c.32033
  8. J Hum Genet. 2023 03;68(3): 113
    Genetics of neurological and psychiatric disorders.
    Tatsushi Toda.
      
    DOI:  https://doi.org/10.1038/s10038-022-01114-0
  9. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2023 Mar 10. 40(3): 364-367
    [A case of Congenital disorder of glycosylation due to SSR4 gene deletion].
    Lingwei Weng, Qingqing Deng, Xiuli Chen, Kai Wang, Jie Shao.
       OBJECTIVE: To explore the clinical and molecular characteristics of a child with Congenital disorders of glycosylation (CDG).
    METHODS: A 4-month-old boy who had presented at the Children's Hospital Affiliated to Zhejiang University Medical School on December 31, 2019 due to feeding difficulties after birth was selected as the study subject. High-throughput sequencing was carried out for the patient, and real-time qPCR was used for validating the suspected deletion fragments and the carrier status of other members of his family.
    RESULTS: High-throughput sequencing revealed that the child had lost the capture signal for chrX: 153 045 645-153 095 809 (approximately 50 kb), which has involved 4 OMIM genes including SRPK3, IDH3G, SSR4 and PDZD4. qPCR verified that the copy number in this region was zero, while that of his elder brother and parents was all normal.
    CONCLUSION: The deletion of the fragment containing the SSR4 gene in the Xq28 region probably underlay the SSR4-CDG in this child.
    DOI:  https://doi.org/10.3760/cma.j.cn511374-20210918-00762
  10. Commun Med (Lond). 2023 Feb 28. 3(1): 20
    Patient engagement and involvement in rare disease research.
      
    DOI:  https://doi.org/10.1038/s43856-023-00251-7
  11. J Med Genet. 2023 Feb 27. pii: jmedgenet-2022-108677. [Epub ahead of print]
    TRAPPC2L-related disorder: first homozygous protein-truncating variant and further delineation of the phenotype.
    Mario Abaji, Cécile Mignon-Ravix, Svetlana Gorokhova, Pierre Cacciagli, Jérémie Mortreux, Florence Molinari, Brigitte Chabrol, Sabine Sigaudy, Laurent Villard, Florence Riccardi.
      The TRAPP (TRAfficking Protein Particle) complexes are evolutionarily conserved tethering factors involved in the intracellular transport of vesicles for secretion and autophagy processes. Pathogenic variants in 8 genes (of 14) encoding TRAPP proteins are involved in ultra-rare human diseases, called TRAPPopathies. Seven of them are autosomal recessive neurodevelopmental disorders with overlapping phenotypes. Since 2018, two homozygous missense variants in TRAPPC2L have been reported in five individuals from three unrelated families with early-onset and progressive encephalopathy, with episodic rhabdomyolysis. We now describe the first pathogenic protein-truncating variant in the TRAPPC2L gene found at a homozygous state in two affected siblings. This report provides key genetic evidence invaluable to establishing the gene-disease relationship for this gene and important insights into the TRAPPC2L phenotype. Regression, seizures and postnatal microcephaly initially described are not constant features. Acute episodes of infection do not contribute to the neurological course. HyperCKaemia is part of the clinical picture. Thus, TRAPPC2L syndrome is mainly characterised by a severe neurodevelopmental disorder and a variable degree of muscle involvement, suggesting that it belongs to the clinical entity of rare congenital muscular dystrophies.
    Keywords:  Genetics, Medical; Mental Disorders; Mutation; Neuromuscular Diseases
    DOI:  https://doi.org/10.1136/jmg-2022-108677
  12. Curr Cardiol Rep. 2023 Feb 28.
    Towards a New Classification of Cardiomyopathies.
    Perry Elliott.
       PURPOSE OF REVIEW: The aim of this paper is to briefly summarise the clinical approach to disease notation for cardiomyopathies and to highlight its limitations with respect to the integration of new knowledge about aetiology.
    RECENT FINDINGS: The paper uses the recently advocated concept of arrhythmogenic cardiomyopathy as an example of the limitations of current classification systems. At present, there is no single classification system that meets the needs of all potential users, whether they are basic scientists, clinicians, patients or families. The classical cardiomyopathy subtypes still have utility, but future disease notation needs to be modified to take into account the new and more complete phenotypes and aetiologies.
    Keywords:  Aetiology; Cardiomyopathy; Classification; Genetic; Molecular; Nosology
    DOI:  https://doi.org/10.1007/s11886-023-01849-y
  13. World J Pediatr Congenit Heart Surg. 2023 Mar 03. 21501351221139837
    Impact of Genetic Disorders in the Surgical Management of Congenital Heart Disease.
    Elizabeth H Stephens, Joseph A Dearani, Heidi M Connolly, Stephen J Gleich, David R Deyle, Jonathan N Johnson.
      The congenital heart surgeon frequently encounters patients with various genetic disorders requiring surgical intervention. Although the specifics of the genetics for these patients and their families lie in the purview of specialists in genetics, the surgeon is well-served to be familiar with aspects of specific syndromes that impact surgical management and perioperative care. This aids in counseling families in expectations for the hospital course and recovery as well as can impact intraoperative and surgical management. This review article summarizes key characteristics for the congenital heart surgeon to be familiar with for common genetic disorders as they help coordinate care.
    Keywords:  congenital heart surgery; genes/polymorphisms; genetics; genomics
    DOI:  https://doi.org/10.1177/21501351221139837
  14. Dis Model Mech. 2023 Feb 01. pii: dmm049874. [Epub ahead of print]16(2):
    New advances in CRISPR/Cas-mediated precise gene-editing techniques.
    Chris Richardson, Robert N Kelsh, Rebecca J Richardson.
      Over the past decade, CRISPR/Cas-based gene editing has become a powerful tool for generating mutations in a variety of model organisms, from Escherichia coli to zebrafish, rodents and large mammals. CRISPR/Cas-based gene editing effectively generates insertions or deletions (indels), which allow for rapid gene disruption. However, a large proportion of human genetic diseases are caused by single-base-pair substitutions, which result in more subtle alterations to protein function, and which require more complex and precise editing to recreate in model systems. Precise genome editing (PGE) methods, however, typically have efficiencies of less than a tenth of those that generate less-specific indels, and so there has been a great deal of effort to improve PGE efficiency. Such optimisations include optimal guide RNA and mutation-bearing donor DNA template design, modulation of DNA repair pathways that underpin how edits result from Cas-induced cuts, and the development of Cas9 fusion proteins that introduce edits via alternative mechanisms. In this Review, we provide an overview of the recent progress in optimising PGE methods and their potential for generating models of human genetic disease.
    Keywords:  Base/prime editing; CRISPR/Cas; HDR; Human disease modelling; Precise genome editing
    DOI:  https://doi.org/10.1242/dmm.049874
  15. Cas Lek Cesk. 2023 ;161(7-8): 271-275
    Ethical principles for the usage and sharing of genomic data from researc.
    Věra Franková, Hana Svozilová, Viktor Stránecký, Kateřina Staňo Kozubík, Josef Srovnal, Lucie Benešová, Magdalena Uvírová, Milan Macek, Šárka Pospíšilová.
      The current significant development of human genome/exome sequencing in biomedical research is one of the important paths leading to personalized medicine. However, sequencing of human genetic information generates potentially sensitive and exploitable data, which leads to ethical, legal, and security issues. For this reason, it is necessary to follow several measures when working with these data, applying to their entire life cycle - i.e., acquisition, storage, processing, usage, sharing, archiving, and reuse. In addition, importance of good practice during the whole data life cycle is emphasized by current European trends towards open science and digital transformation. Therefore, the following recommendations have been developed, establishing principles for work with the whole human genome sequences or parts of it in research context. The recommendations are based on two documents published by the Global Alliance for Genomics and Health (GA4GH) and on foreign literature, thus summarizing recent relevant guidance on most aspects of working with human genomic data.
    Keywords:  Genomics; data sharing; ethics; genomics; guidelines; standards
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