Mohr-Tranebjærg syndrome is an X-linked syndrome characterized by sensorineural hearing impairment in childhood, followed by progressive neurodegeneration leading to a broad phenotypic spectrum. Genetically MTS is caused by pathogenic variants in the TIMM8A gene, including gene deletions and larger contiguous gene deletions. Some of the latter involve the neighboring gene BTK, resulting in agammaglobulinemia. By next‐generation mate‐pair sequencing we have mapped the chromosomal deletion breakpoints of one MTS case and three XLA-MTS cases and used breakpoint-spanning PCR to fine map the breakpoints by Sanger sequencing. Two of the XLA-MTS cases presented with large deletions (63.5 and 27.2 kb), and the junctional regions were characterized by long stretches of microhomology, indicating that the events have emerged through homologous recombination. Conversely, the MTS case exhibited a small 2 bp region of microhomology, and the regions were not characterized by extensive microhomology. The third XLA-MTS case had a more complex breakpoint, including a 59 bp inverted insertion, thus at least four breakpoints were involved in this event. In conclusion, mate-pair library generation combined with next-generation sequencing is an efficient method for breakpoint identification, also in regions characterized by repetitive elements.

Rendtorff N.D., Karstensen H.G., Lodahl M., Tolmie J., McWilliam C., Bak M., et al. (2022). Identification and analysis of deletion breakpoints in four Mohr-Tranebjærg syndrome (MTS) patients. SCIENTIFIC REPORTS, 12(1), 1-7 [10.1038/s41598-022-18040-y].

Identification and analysis of deletion breakpoints in four Mohr-Tranebjærg syndrome (MTS) patients

Carelli V.;
2022

Abstract

Mohr-Tranebjærg syndrome is an X-linked syndrome characterized by sensorineural hearing impairment in childhood, followed by progressive neurodegeneration leading to a broad phenotypic spectrum. Genetically MTS is caused by pathogenic variants in the TIMM8A gene, including gene deletions and larger contiguous gene deletions. Some of the latter involve the neighboring gene BTK, resulting in agammaglobulinemia. By next‐generation mate‐pair sequencing we have mapped the chromosomal deletion breakpoints of one MTS case and three XLA-MTS cases and used breakpoint-spanning PCR to fine map the breakpoints by Sanger sequencing. Two of the XLA-MTS cases presented with large deletions (63.5 and 27.2 kb), and the junctional regions were characterized by long stretches of microhomology, indicating that the events have emerged through homologous recombination. Conversely, the MTS case exhibited a small 2 bp region of microhomology, and the regions were not characterized by extensive microhomology. The third XLA-MTS case had a more complex breakpoint, including a 59 bp inverted insertion, thus at least four breakpoints were involved in this event. In conclusion, mate-pair library generation combined with next-generation sequencing is an efficient method for breakpoint identification, also in regions characterized by repetitive elements.
2022
Rendtorff N.D., Karstensen H.G., Lodahl M., Tolmie J., McWilliam C., Bak M., et al. (2022). Identification and analysis of deletion breakpoints in four Mohr-Tranebjærg syndrome (MTS) patients. SCIENTIFIC REPORTS, 12(1), 1-7 [10.1038/s41598-022-18040-y].
Rendtorff N.D.; Karstensen H.G.; Lodahl M.; Tolmie J.; McWilliam C.; Bak M.; Tommerup N.; Nazaryan-Petersen L.; Kunst H.; Wong M.; Joss S.; Carelli V....espandi
File in questo prodotto:
File Dimensione Formato  
s41598-022-18040-y (1).pdf

accesso aperto

Tipo: Versione (PDF) editoriale
Licenza: Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY)
Dimensione 1.75 MB
Formato Adobe PDF
1.75 MB Adobe PDF Visualizza/Apri
41598_2022_18040_MOESM1_ESM.docx

accesso aperto

Tipo: File Supplementare
Licenza: Licenza per accesso libero gratuito
Dimensione 26.88 kB
Formato Microsoft Word XML
26.88 kB Microsoft Word XML Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/903023
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 2
social impact