Universität zu Köln

Keller, Natalie, Paketci, Cem, Altmueller, Janine, Fuhrmann, Nico, Wunderlich, Gilbert, Schrank, Bertold, Unver, Olcay, Yilmaz, Sanem, Boostani, Reza, Karimiani, Ehsan Ghayoor, Motameny, Susanne, Thiele, Holger, Nuernberg, Peter, Maroofian, Reza, Yis, Uluc, Wirth, Brunhilde ORCID: 0000-0003-4051-5191 and Karakaya, Mert (2021). Genomic variants causing mitochondrial dysfunction are common in hereditary lower motor neuron disease. Hum. Mutat., 42 (4). S. 460 - 473. HOBOKEN: WILEY. ISSN 1098-1004

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Abstract

Hereditary lower motor neuron diseases (LMND) other than 5q-spinal muscular atrophy (5q-SMA) can be classified according to affected muscle groups. Proximal and distal forms of non-5q-SMA represent a clinically and genetically heterogeneous spectrum characterized by significant overlaps with axonal forms of Charcot-Marie-Tooth (CMT) disease. A consensus for the best approach to molecular diagnosis needs to be reached, especially in light of continuous novel gene discovery and falling costs of next-generation sequencing (NGS). We performed exome sequencing (ES) in 41 families presenting with non-5q-SMA or axonal CMT, 25 of which had undergone a previous negative neuromuscular disease (NMD) gene panel analysis. The total diagnostic yield of ES was 41%. Diagnostic success in the cohort with a previous NMD-panel analysis was significantly extended by ES, primarily due to novel gene associated-phenotypes and uncharacteristic phenotypic presentations. We recommend early ES for individuals with hereditary LMND presenting uncharacteristic or significantly overlapping features. As mitochondrial dysfunction was the underlying pathomechanism in 47% of the solved individuals, we highlight the sensitivity of the anterior horn cell and peripheral nerve to mitochondrial imbalance as well as the necessity to screen for mitochondrial disorders in individuals presenting predominant lower motor neuron symptoms.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Keller, Natalie UNSPECIFIED UNSPECIFIED UNSPECIFIED Paketci, Cem UNSPECIFIED UNSPECIFIED UNSPECIFIED Altmueller, Janine UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuhrmann, Nico UNSPECIFIED UNSPECIFIED UNSPECIFIED Wunderlich, Gilbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Schrank, Bertold UNSPECIFIED UNSPECIFIED UNSPECIFIED Unver, Olcay UNSPECIFIED UNSPECIFIED UNSPECIFIED Yilmaz, Sanem UNSPECIFIED UNSPECIFIED UNSPECIFIED Boostani, Reza UNSPECIFIED UNSPECIFIED UNSPECIFIED Karimiani, Ehsan Ghayoor UNSPECIFIED UNSPECIFIED UNSPECIFIED Motameny, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Thiele, Holger UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Maroofian, Reza UNSPECIFIED UNSPECIFIED UNSPECIFIED Yis, Uluc UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirth, Brunhilde UNSPECIFIED orcid.org/0000-0003-4051-5191 UNSPECIFIED Karakaya, Mert UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-597863
DOI:	10.1002/humu.24181
Journal or Publication Title:	Hum. Mutat.
Volume:	42
Number:	4
Page Range:	S. 460 - 473
Date:	2021
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1098-1004
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59786