{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T05:54:52Z","timestamp":1793253292807,"version":"4.5.0"},"reference-count":21,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Heterozygous gain-of-function variants in SAMD9L are associated with ataxia-pancytopenia syndrome (ATXPC) and monosomy 7 myelodysplasia and leukemia syndrome-1 (M7MLS1). Association with peripheral neuropathy has rarely been described. Methods: Whole-exome sequencing (WES) from DNA extracted from peripheral blood was performed in a 10-year-old female presenting with demyelinating neuropathy, her similarly affected mother and the unaffected maternal grandparents. In addition to evaluation of single nucleotide variants, thorough work-up of copy number and exome-wide variant allele frequency data was performed. Results: Combined analysis of the mother\u2019s and daughter\u2019s duo-exome data and analysis of the mother\u2019s and her parents\u2019 trio-exome data initially failed to detect a disease-associated variant. More detailed analysis revealed a copy number neutral loss of heterozygosity of 7q in the mother and led to reanalysis of the exome data for respective sequence variants. Here, a previously reported likely pathogenic variant in the SAMD9L gene on chromosome 7q (NM_152703.5:c.2956C&gt;T; p.(Arg986Cys)) was identified that was not detected with standard filter settings because of a low percentage in blood cells (13%). The variant also showed up in the daughter at 32%, a proportion well below the expected 50%, which in each case can be explained by clonal selection processes in the blood due to this SAMD9L variant. Conclusion: The report highlights the specific pitfalls of molecular genetic analysis of SAMD9L and, furthermore, shows that gain-of-function variants in this gene can lead to a clinical picture associated with the leading symptom of peripheral neuropathy. Due to clonal hematopoietic selection, displacement of the mutant allele occurred, making diagnosis difficult.<\/jats:p>","DOI":"10.3390\/genes13122356","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T02:54:21Z","timestamp":1670986461000},"page":"2356","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Clonal Elimination of the Pathogenic Allele as Diagnostic Pitfall in SAMD9L-Associated Neuropathy"],"prefix":"10.3390","volume":"13","author":[{"given":"K.","family":"Eggermann","sequence":"first","affiliation":[{"name":"Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5693-2216","authenticated-orcid":false,"given":"R.","family":"Meyer","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4659-8437","authenticated-orcid":false,"given":"M.","family":"Begemann","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Dey","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"B\u00fcltmann","sequence":"additional","affiliation":[{"name":"Institute of Diagnostic and Interventional Neuroradiology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Kurth","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. C.","family":"Korenke","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics, University Children\u2019s Hospital, Klinikum Oldenburg, 26133 Oldenburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Knopp","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics and Genomic Medicine, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1038\/s41467-017-01590-5","article-title":"The genomic landscape of pediatric myelodysplastic syndromes","volume":"8","author":"Schwartz","year":"2017","journal-title":"Nat. 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