PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Kleinle, S.* ; Scholz, V.* ; Benet-Pages, A. ; Wohlfrom, T.* ; Gehling, S.* ; Scharf, F.* ; Rost, S.* ; Prott, E.C.* ; Grinzinger, S.* ; Hotter, A.* ; Haug, V.* ; Niemeier, S.* ; Wiethoff-Ubrig, L.* ; Hagenacker, T.* ; Goldhahn, K.* ; von Moers, A.* ; Walter, M.* ; Reilich, P.* ; Eggermann, K.* ; Kraft, F.* ; Kurth, I.* ; Erdmann, H.* ; Holinski-Feder, E.* ; Neuhann, T.* ; Abicht, A.*

Closing the Gap - Detection of 5q-spinal muscular atrophy by short-read Next-generation sequencing and unexpected results in a diagnostic patient cohort.

J. Neuromuscul. Dis. 10, 835-846 (2023)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
BACKGROUND: The importance of early diagnosis of 5q-Spinal muscular atrophy (5q-SMA) has heightened as early intervention can significantly improve clinical outcomes. In 96% of cases, 5q-SMA is caused by a homozygous deletion of SMN1. Around 4 % of patients carry a SMN1 deletion and a single-nucleotide variant (SNV) on the other allele. Traditionally, diagnosis is based on multiplex ligation probe amplification (MLPA) to detect homozygous or heterozygous exon 7 deletions in SMN1. Due to high homologies within the SMN1/SMN2 locus, sequence analysis to identify SNVs of the SMN1 gene is unreliable by standard Sanger or short-read next-generation sequencing (srNGS) methods. OBJECTIVE: The objective was to overcome the limitations in high-throughput srNGS with the aim of providing SMA patients with a fast and reliable diagnosis to enable their timely therapy. METHODS: A bioinformatics workflow to detect homozygous SMN1 deletions and SMN1 SNVs on srNGS analysis was applied to diagnostic whole exome and panel testing for suggested neuromuscular disorders (1684 patients) and to fetal samples in prenatal diagnostics (260 patients). SNVs were detected by aligning sequencing reads from SMN1 and SMN2 to an SMN1 reference sequence. Homozygous SMN1 deletions were identified by filtering sequence reads for the ,, gene-determining variant" (GDV). RESULTS: 10 patients were diagnosed with 5q-SMA based on (i) SMN1 deletion and hemizygous SNV (2 patients), (ii) homozygous SMN1 deletion (6 patients), and (iii) compound heterozygous SNVs in SMN1 (2 patients). CONCLUSIONS: Applying our workflow in srNGS-based panel and whole exome sequencing (WES) is crucial in a clinical laboratory, as otherwise patients with an atypical clinical presentation initially not suspected to suffer from SMA remain undiagnosed.
Impact Factor
Scopus SNIP
Altmetric
3.300
0.000
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter 5q-sma ; Bioninformatics ; Clinical Genetics ; Dark Genes ; Neuromuscular Disorders ; Spinal Muscular Atrophy; Management; Genomics
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
ISSN (print) / ISBN 2214-3599
e-ISSN 2214-3602
Zeitschrift Journal of neuromuscular diseases
Quellenangaben Band: 10, Heft: 5, Seiten: 835-846 Artikelnummer: , Supplement: ,
Verlag IOS Press
Verlagsort Amsterdam
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Neurogenomics (ING)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-503200-001
Förderungen Medical Genetic Center
DOI 10.3233/JND-221668
WOS ID 001067500200008
Scopus ID 85170581931
PubMed ID 37424474
Erfassungsdatum 2023-10-06
[➜Korrektur melden]