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GAA variants associated with reduced enzymatic activity but lack of Pompe-related symptoms, incidentally identified by exome sequencing.
Malekkou, Anna; Theodosiou, Athina; Alexandrou, Angelos; Papaevripidou, Ioannis; Sismani, Carolina; Jacobs, Edwin H; Ruijter, George J G; Anastasiadou, Violetta; Ourani, Sofia; Athanasiou, Emilia; Drousiotou, Anthi; Grafakou, Olga; Petrou, Petros P.
Afiliación
  • Malekkou A; Biochemical Genetics Department, The Cyprus Institute of Neurology and Genetics, P. O. Box 23462, 1683 Nicosia, Cyprus.
  • Theodosiou A; Cytogenetics and Genomics Department, The Cyprus Institute of Neurology and Genetics, P. O. Box 23462, 1683 Nicosia, Cyprus.
  • Alexandrou A; Cytogenetics and Genomics Department, The Cyprus Institute of Neurology and Genetics, P. O. Box 23462, 1683 Nicosia, Cyprus.
  • Papaevripidou I; Cytogenetics and Genomics Department, The Cyprus Institute of Neurology and Genetics, P. O. Box 23462, 1683 Nicosia, Cyprus.
  • Sismani C; Cytogenetics and Genomics Department, The Cyprus Institute of Neurology and Genetics, P. O. Box 23462, 1683 Nicosia, Cyprus.
  • Jacobs EH; Center for Lysosomal and Metabolic Diseases, Department of Clinical Genetics, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands.
  • Ruijter GJG; Center for Lysosomal and Metabolic Diseases, Department of Clinical Genetics, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015, GD, Rotterdam, the Netherlands.
  • Anastasiadou V; Clinical Genetics Department, Archbishop Makarios III Hospital, Korytsas 6, 2012 Nicosia, Cyprus.
  • Ourani S; Karaiskakio Foundation, P.O. Box 22680, 1523 Nicosia, Cyprus.
  • Athanasiou E; Clinical Genetics Department, Archbishop Makarios III Hospital, Korytsas 6, 2012 Nicosia, Cyprus.
  • Drousiotou A; Clinical Genetics Department, Archbishop Makarios III Hospital, Korytsas 6, 2012 Nicosia, Cyprus.
  • Grafakou O; Biochemical Genetics Department, The Cyprus Institute of Neurology and Genetics, P. O. Box 23462, 1683 Nicosia, Cyprus.
  • Petrou PP; Inborn Errors of Metabolism Clinic, Department of Pediatrics, Archbishop Makarios III Hospital, Korytsas 6, 2012 Nicosia, Cyprus.
Mol Genet Metab Rep ; 36: 100997, 2023 Sep.
Article en En | MEDLINE | ID: mdl-37600231
Pompe disease is a rare metabolic myopathy caused by pathogenic variants affecting the activity of the lysosomal glycogen-degrading enzyme acid alpha-glucosidase (GAA). Impaired GAA function results in the accumulation of undegraded glycogen within lysosomes in multiple tissues but predominantly affects the skeletal, smooth and cardiac muscle. The degree of residual enzymatic activity appears to roughly correlate with the age of onset and the severity of the clinical symptoms. Here, we report four siblings in which the GAA variants NM_000152.5:c.2237G > C p.(Trp746Ser) and NM_000152.5:c.266G > A p.(Arg89His) were identified as an incidental finding of clinical exome sequencing. These variants are listed in the ClinVar and the Pompe disease GAA variant databases but are reported here for the first time in compound heterozygosity. All four siblings displayed normal urine tetrasaccharide levels and no clinical manifestations related to Pompe disease. Nevertheless, GAA enzymatic activity was within the range for late onset Pompe patients. Our report shows an association between a novel genotype and attenuated GAA enzymatic activity. The clinical significance can only be established by the regular monitoring of these individuals. The study highlights the major challenges for clinical care arising from incidental findings of next generation sequencing.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Mol Genet Metab Rep Año: 2023 Tipo del documento: Article País de afiliación: Chipre Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Mol Genet Metab Rep Año: 2023 Tipo del documento: Article País de afiliación: Chipre Pais de publicación: Estados Unidos