Early detection of lysosomal diseases by screening of cases of idiopathic splenomegaly and/or thrombocytopenia with a next‐generation sequencing gene panel
Abstract Lysosomal diseases (LD) are a group of about 70 rare hereditary disorders (combined incidence 1:5000) in which diverse lysosomal functions are impaired, impacting multiple organs and systems. The first clinical signs and symptoms are usually unspecific and shared by hundreds of other disord...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | JIMD Reports |
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| Online Access: | https://doi.org/10.1002/jmd2.12078 |
| _version_ | 1811265942463709184 |
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| author | Gloria Muñoz David García‐Seisdedos Crina Ciubotariu Miguel Piris‐Villaespesa Marta Gandía Fernando Martín‐Moro Luis G. Gutiérrez‐Solana Marta Morado Javier López‐Jiménez Antonio Sánchez‐Herranz Jesús Villarrubia Francisco J. delCastillo |
| author_facet | Gloria Muñoz David García‐Seisdedos Crina Ciubotariu Miguel Piris‐Villaespesa Marta Gandía Fernando Martín‐Moro Luis G. Gutiérrez‐Solana Marta Morado Javier López‐Jiménez Antonio Sánchez‐Herranz Jesús Villarrubia Francisco J. delCastillo |
| author_sort | Gloria Muñoz |
| collection | DOAJ |
| description | Abstract Lysosomal diseases (LD) are a group of about 70 rare hereditary disorders (combined incidence 1:5000) in which diverse lysosomal functions are impaired, impacting multiple organs and systems. The first clinical signs and symptoms are usually unspecific and shared by hundreds of other disorders. Diagnosis of LD traditionally relies on performing specific enzymatic assays, if available, upon clinical suspicion of the disorder. However, the combination of the insidious onset of LD and the lack of awareness on these rare diseases among medical personnel results in undesirable diagnostic delays, with unchecked disease progression, appearance of complications and a worsened prognosis. We tested the usefulness of a next‐generation sequencing‐based gene panel for quick, early detection of LD among cases of idiopathic splenomegaly and/or thrombocytopenia, two of the earliest clinical signs observed in most LD. Our 73‐gene panel interrogated 28 genes for LD, 1 biomarker and 44 genes underlying non‐LD differential diagnoses. Among 38 unrelated patients, we elucidated eight cases (21%), five with LD (GM1 gangliosidosis, Sanfilippo disease A and B, Niemann‐Pick disease B, Gaucher disease) and three with non‐LD conditions. Interestingly, we identified three LD patients harboring pathogenic mutations in two LD genes each, which may result in unusual disease presentations and impact treatment. Turnaround time for panel screening and genetic validation was 1 month. Our results underline the usefulness of resequencing gene panels for quick and cost‐effective screening of LDs and disorders sharing with them early clinical signs. |
| first_indexed | 2024-04-12T20:33:02Z |
| format | Article |
| id | doaj.art-95ca803243314fdd818ceecd749c97f9 |
| institution | Directory Open Access Journal |
| issn | 2192-8312 |
| language | English |
| last_indexed | 2024-04-12T20:33:02Z |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | JIMD Reports |
| spelling | doaj.art-95ca803243314fdd818ceecd749c97f92022-12-22T03:17:41ZengWileyJIMD Reports2192-83122020-01-01511536110.1002/jmd2.12078Early detection of lysosomal diseases by screening of cases of idiopathic splenomegaly and/or thrombocytopenia with a next‐generation sequencing gene panelGloria Muñoz0David García‐Seisdedos1Crina Ciubotariu2Miguel Piris‐Villaespesa3Marta Gandía4Fernando Martín‐Moro5Luis G. Gutiérrez‐Solana6Marta Morado7Javier López‐Jiménez8Antonio Sánchez‐Herranz9Jesús Villarrubia10Francisco J. delCastillo11UCA de Genómica Traslacional Hospital Universitario Ramón y Cajal, IRYCIS Madrid SpainUCA de Genómica Traslacional Hospital Universitario Ramón y Cajal, IRYCIS Madrid SpainUCA de Genómica Traslacional Hospital Universitario Ramón y Cajal, IRYCIS Madrid SpainServicio de Hematología Hospital Universitario Ramón y Cajal, IRYCIS Madrid SpainUCA de Genómica Traslacional Hospital Universitario Ramón y Cajal, IRYCIS Madrid SpainServicio de Hematología Hospital Universitario Ramón y Cajal, IRYCIS Madrid SpainConsulta de Neurodegenerativas, Servicio de Neurología Pediátrica Hospital Infantil Universitario Niño Jesús Madrid SpainServicio de Hematología Hospital Universitario La Paz Madrid SpainServicio de Hematología Hospital Universitario Ramón y Cajal, IRYCIS Madrid SpainUCA de Genómica Traslacional Hospital Universitario Ramón y Cajal, IRYCIS Madrid SpainUCA de Genómica Traslacional Hospital Universitario Ramón y Cajal, IRYCIS Madrid SpainUCA de Genómica Traslacional Hospital Universitario Ramón y Cajal, IRYCIS Madrid SpainAbstract Lysosomal diseases (LD) are a group of about 70 rare hereditary disorders (combined incidence 1:5000) in which diverse lysosomal functions are impaired, impacting multiple organs and systems. The first clinical signs and symptoms are usually unspecific and shared by hundreds of other disorders. Diagnosis of LD traditionally relies on performing specific enzymatic assays, if available, upon clinical suspicion of the disorder. However, the combination of the insidious onset of LD and the lack of awareness on these rare diseases among medical personnel results in undesirable diagnostic delays, with unchecked disease progression, appearance of complications and a worsened prognosis. We tested the usefulness of a next‐generation sequencing‐based gene panel for quick, early detection of LD among cases of idiopathic splenomegaly and/or thrombocytopenia, two of the earliest clinical signs observed in most LD. Our 73‐gene panel interrogated 28 genes for LD, 1 biomarker and 44 genes underlying non‐LD differential diagnoses. Among 38 unrelated patients, we elucidated eight cases (21%), five with LD (GM1 gangliosidosis, Sanfilippo disease A and B, Niemann‐Pick disease B, Gaucher disease) and three with non‐LD conditions. Interestingly, we identified three LD patients harboring pathogenic mutations in two LD genes each, which may result in unusual disease presentations and impact treatment. Turnaround time for panel screening and genetic validation was 1 month. Our results underline the usefulness of resequencing gene panels for quick and cost‐effective screening of LDs and disorders sharing with them early clinical signs.https://doi.org/10.1002/jmd2.12078genetic screeninglysosomal diseaseNGS resequencing panelssplenomegalythrombocytopenia |
| spellingShingle | Gloria Muñoz David García‐Seisdedos Crina Ciubotariu Miguel Piris‐Villaespesa Marta Gandía Fernando Martín‐Moro Luis G. Gutiérrez‐Solana Marta Morado Javier López‐Jiménez Antonio Sánchez‐Herranz Jesús Villarrubia Francisco J. delCastillo Early detection of lysosomal diseases by screening of cases of idiopathic splenomegaly and/or thrombocytopenia with a next‐generation sequencing gene panel JIMD Reports genetic screening lysosomal disease NGS resequencing panels splenomegaly thrombocytopenia |
| title | Early detection of lysosomal diseases by screening of cases of idiopathic splenomegaly and/or thrombocytopenia with a next‐generation sequencing gene panel |
| title_full | Early detection of lysosomal diseases by screening of cases of idiopathic splenomegaly and/or thrombocytopenia with a next‐generation sequencing gene panel |
| title_fullStr | Early detection of lysosomal diseases by screening of cases of idiopathic splenomegaly and/or thrombocytopenia with a next‐generation sequencing gene panel |
| title_full_unstemmed | Early detection of lysosomal diseases by screening of cases of idiopathic splenomegaly and/or thrombocytopenia with a next‐generation sequencing gene panel |
| title_short | Early detection of lysosomal diseases by screening of cases of idiopathic splenomegaly and/or thrombocytopenia with a next‐generation sequencing gene panel |
| title_sort | early detection of lysosomal diseases by screening of cases of idiopathic splenomegaly and or thrombocytopenia with a next generation sequencing gene panel |
| topic | genetic screening lysosomal disease NGS resequencing panels splenomegaly thrombocytopenia |
| url | https://doi.org/10.1002/jmd2.12078 |
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