De novo pathogenic DNM1L variant in a patient diagnosed with atypical hereditary sensory and autonomic neuropathy

Abstract Background Profiling the entire genome at base pair resolution in a single test offers novel insights into disease by means of dissection of genetic contributors to phenotypic features. Methods We performed genome sequencing for a patient who presented with atypical hereditary sensory and a...

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Main Authors:	Maja Tarailo‐Graovac, Farah R. Zahir, Irena Zivkovic, Michelle Moksa, Kathryn Selby, Sunita Sinha, Corey Nislow, Sylvia G. Stockler‐Ipsiroglu, Ruth Sheffer, Ann Saada‐Reisch, Jan M. Friedman, Clara D. M. vanKarnebeek, Gabriella A. Horvath
Format:	Article
Language:	English
Published:	Wiley 2019-10-01
Series:	Molecular Genetics & Genomic Medicine
Subjects:	DNM1L epileptic encephalopathy HSAN intradermal histamine test self‐injury whole genome sequencing
Online Access:	https://doi.org/10.1002/mgg3.961

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record_format	Article
spelling	doaj-431df59ffec0495999ad7c1a0e1e78572020-11-25T01:23:25ZengWileyMolecular Genetics & Genomic Medicine2324-92692019-10-01710n/an/a10.1002/mgg3.961De novo pathogenic DNM1L variant in a patient diagnosed with atypical hereditary sensory and autonomic neuropathyMaja Tarailo‐Graovac0Farah R. Zahir1Irena Zivkovic2Michelle Moksa3Kathryn Selby4Sunita Sinha5Corey Nislow6Sylvia G. Stockler‐Ipsiroglu7Ruth Sheffer8Ann Saada‐Reisch9Jan M. Friedman10Clara D. M. vanKarnebeek11Gabriella A. Horvath12Centre for Molecular Medicine and Therapeutics BC Children's Research Institute University of British Columbia Vancouver CanadaDepartment of Medical Genetics University of British Columbia Vancouver CanadaUniversity of British Columbia Vancouver CanadaDepartment of Microbiology and Immunology University of British Columbia Vancouver CanadaDepartment of Pediatrics Division of Pediatric Neurology University of British Columbia Vancouver CanadaFaculty of Pharmaceutical Sciences University of British Columbia Vancouver CanadaFaculty of Pharmaceutical Sciences University of British Columbia Vancouver CanadaDepartment of Pediatrics Division of Biochemical Diseases University of British Columbia Vancouver CanadaDepartment of Genetics and Metabolic Diseases Hadassah‐Hebrew University Medical Center Jerusalem IsraelDepartment of Genetics and Metabolic Diseases Hadassah‐Hebrew University Medical Center Jerusalem IsraelDepartment of Medical Genetics University of British Columbia Vancouver CanadaDepartment of Pediatrics Centre for Molecular Medicine and Therapeutics BC Children's Research Institute University of British Columbia Vancouver CanadaDepartment of Pediatrics Division of Biochemical Diseases University of British Columbia Vancouver CanadaAbstract Background Profiling the entire genome at base pair resolution in a single test offers novel insights into disease by means of dissection of genetic contributors to phenotypic features. Methods We performed genome sequencing for a patient who presented with atypical hereditary sensory and autonomic neuropathy, severe epileptic encephalopathy, global developmental delay, and growth hormone deficiency. Results Assessment of the variants detected by mapped sequencing reads followed by Sanger confirmation revealed that the proband is a compound heterozygote for rare variants within RETREG1 (FAM134B), a gene associated with a recessive form of hereditary sensory and autonomic neuropathy, but not with epileptic encephalopathy or global developmental delay. Further analysis of the data also revealed a heterozygous missense variant in DNM1L, a gene previously implicated in an autosomal dominant encephalopathy, epilepsy, and global developmental delay and confirmed by Sanger sequencing to be a de novo variant not present in parental genomes. Conclusions Our findings emphasize the importance of genome‐wide sequencing in patients with a well‐characterized genetic disease with atypical presentation. This approach reduces the potential for misdiagnoses.https://doi.org/10.1002/mgg3.961DNM1Lepileptic encephalopathyHSANintradermal histamine testself‐injurywhole genome sequencing
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Maja Tarailo‐Graovac Farah R. Zahir Irena Zivkovic Michelle Moksa Kathryn Selby Sunita Sinha Corey Nislow Sylvia G. Stockler‐Ipsiroglu Ruth Sheffer Ann Saada‐Reisch Jan M. Friedman Clara D. M. vanKarnebeek Gabriella A. Horvath
spellingShingle	Maja Tarailo‐Graovac Farah R. Zahir Irena Zivkovic Michelle Moksa Kathryn Selby Sunita Sinha Corey Nislow Sylvia G. Stockler‐Ipsiroglu Ruth Sheffer Ann Saada‐Reisch Jan M. Friedman Clara D. M. vanKarnebeek Gabriella A. Horvath De novo pathogenic DNM1L variant in a patient diagnosed with atypical hereditary sensory and autonomic neuropathy Molecular Genetics & Genomic Medicine DNM1L epileptic encephalopathy HSAN intradermal histamine test self‐injury whole genome sequencing
author_facet	Maja Tarailo‐Graovac Farah R. Zahir Irena Zivkovic Michelle Moksa Kathryn Selby Sunita Sinha Corey Nislow Sylvia G. Stockler‐Ipsiroglu Ruth Sheffer Ann Saada‐Reisch Jan M. Friedman Clara D. M. vanKarnebeek Gabriella A. Horvath
author_sort	Maja Tarailo‐Graovac
title	De novo pathogenic DNM1L variant in a patient diagnosed with atypical hereditary sensory and autonomic neuropathy
title_short	De novo pathogenic DNM1L variant in a patient diagnosed with atypical hereditary sensory and autonomic neuropathy
title_full	De novo pathogenic DNM1L variant in a patient diagnosed with atypical hereditary sensory and autonomic neuropathy
title_fullStr	De novo pathogenic DNM1L variant in a patient diagnosed with atypical hereditary sensory and autonomic neuropathy
title_full_unstemmed	De novo pathogenic DNM1L variant in a patient diagnosed with atypical hereditary sensory and autonomic neuropathy
title_sort	de novo pathogenic dnm1l variant in a patient diagnosed with atypical hereditary sensory and autonomic neuropathy
publisher	Wiley
series	Molecular Genetics & Genomic Medicine
issn	2324-9269
publishDate	2019-10-01
description	Abstract Background Profiling the entire genome at base pair resolution in a single test offers novel insights into disease by means of dissection of genetic contributors to phenotypic features. Methods We performed genome sequencing for a patient who presented with atypical hereditary sensory and autonomic neuropathy, severe epileptic encephalopathy, global developmental delay, and growth hormone deficiency. Results Assessment of the variants detected by mapped sequencing reads followed by Sanger confirmation revealed that the proband is a compound heterozygote for rare variants within RETREG1 (FAM134B), a gene associated with a recessive form of hereditary sensory and autonomic neuropathy, but not with epileptic encephalopathy or global developmental delay. Further analysis of the data also revealed a heterozygous missense variant in DNM1L, a gene previously implicated in an autosomal dominant encephalopathy, epilepsy, and global developmental delay and confirmed by Sanger sequencing to be a de novo variant not present in parental genomes. Conclusions Our findings emphasize the importance of genome‐wide sequencing in patients with a well‐characterized genetic disease with atypical presentation. This approach reduces the potential for misdiagnoses.
topic	DNM1L epileptic encephalopathy HSAN intradermal histamine test self‐injury whole genome sequencing
url	https://doi.org/10.1002/mgg3.961
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De novo pathogenic DNM1L variant in a patient diagnosed with atypical hereditary sensory and autonomic neuropathy

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