PMID- 37686372
OWN - NLM
STAT- MEDLINE
DCOM- 20230919
LR  - 20230919
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 24
IP  - 17
DP  - 2023 Sep 1
TI  - Whole-Genome Sequencing Identified New Structural Variations in the DMD Gene That 
      Cause Duchenne Muscular Dystrophy in Two Girls.
LID - 10.3390/ijms241713567 [doi]
LID - 13567
AB  - Dystrophinopathies are the most common muscle diseases, especially in men. In 
      women, on the other hand, a manifestation of Duchenne muscular dystrophy is rare 
      due to X-chromosomal inheritance. We present two young girls with severe muscle 
      weakness, muscular dystrophies, and creatine kinase (CK) levels exceeding 10,000 
      U/L. In the skeletal muscle tissues, dystrophin staining reaction showed 
      mosaicism. The almost entirely skewed X-inactivation in both cases supported the 
      possibility of a dystrophinopathy. Despite standard molecular diagnostics 
      (including multiplex ligation-dependent probe amplification (MLPA) and next 
      generation sequencing (NGS) gene panel sequencing), the genetic cause of the 
      girls' conditions remained unknown. However, whole-genome sequencing revealed two 
      reciprocal translocations between their X chromosomes and chromosome 5 and 
      chromosome 19, respectively. In both cases, the breakpoints on the X chromosomes 
      were located directly within the DMD gene (in introns 54 and 7, respectively) and 
      were responsible for the patients' phenotypes. Additional techniques such as 
      Sanger sequencing, conventional karyotyping and fluorescence in situ 
      hybridization (FISH) confirmed the disruption of DMD gene in both patients 
      through translocations. These findings underscore the importance of accurate 
      clinical data combined with histopathological analysis in pinpointing the 
      suspected underlying genetic disorder. Moreover, our study illustrates the 
      viability of whole-genome sequencing as a time-saving and highly effective method 
      for identifying genetic factors responsible for complex genetic constellations in 
      Duchenne muscular dystrophy (DMD).
FAU - Pluta, Natalie
AU  - Pluta N
AD  - Department of Human Genetics, University of Wurzburg, 97074 Wurzburg, Germany.
FAU - von Moers, Arpad
AU  - von Moers A
AD  - Department of Pediatrics and Neuropediatrics, DRK Kliniken Berlin, 14050 Berlin, 
      Germany.
FAU - Pechmann, Astrid
AU  - Pechmann A
AD  - Department of Neuropediatrics and Muscle Disorders, Medical Center-University of 
      Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
FAU - Stenzel, Werner
AU  - Stenzel W
AD  - Department of Neuropathology, Charite-Universitatsmedizin Berlin, Corporate 
      Member of Freie Universitat Berlin and Humboldt Universitat zu Berlin, 10117 
      Berlin, Germany.
FAU - Goebel, Hans-Hilmar
AU  - Goebel HH
AD  - Department of Neuropathology, Charite-Universitatsmedizin Berlin, Corporate 
      Member of Freie Universitat Berlin and Humboldt Universitat zu Berlin, 10117 
      Berlin, Germany.
FAU - Atlan, David
AU  - Atlan D
AUID- ORCID: 0000-0002-7001-6644
AD  - Phenosystems SA, 1807 Blonay, Switzerland.
FAU - Wolf, Beat
AU  - Wolf B
AUID- ORCID: 0000-0002-9307-7212
AD  - iCoSys, University of Applied Sciences Western Switzerland, 1700 Fribourg, 
      Switzerland.
FAU - Nanda, Indrajit
AU  - Nanda I
AD  - Department of Human Genetics, University of Wurzburg, 97074 Wurzburg, Germany.
FAU - Zaum, Ann-Kathrin
AU  - Zaum AK
AD  - Department of Human Genetics, University of Wurzburg, 97074 Wurzburg, Germany.
FAU - Rost, Simone
AU  - Rost S
AD  - Department of Human Genetics, University of Wurzburg, 97074 Wurzburg, Germany.
AD  - Medical Genetics Center (MGZ), 80335 Munich, Germany.
LA  - eng
GR  - 444748124/Deutsche Forschungsgemeinschaft/
PT  - Journal Article
DEP - 20230901
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (DMD protein, human)
SB  - IM
MH  - Female
MH  - Humans
MH  - Male
MH  - In Situ Hybridization, Fluorescence
MH  - Introns
MH  - Mosaicism
MH  - Muscle, Skeletal
MH  - *Muscular Dystrophy, Duchenne/diagnosis/genetics
PMC - PMC10488134
OTO - NOTNLM
OT  - DMD
OT  - Duchenne muscular dystrophy
OT  - WGS
OT  - X-inactivation
OT  - structural variants
OT  - translocation
OT  - whole-genome sequencing
COIS- The authors declare no conflict of interest.
EDAT- 2023/09/09 11:43
MHDA- 2023/09/11 06:42
PMCR- 2023/09/01
CRDT- 2023/09/09 01:13
PHST- 2023/08/07 00:00 [received]
PHST- 2023/08/28 00:00 [revised]
PHST- 2023/08/29 00:00 [accepted]
PHST- 2023/09/11 06:42 [medline]
PHST- 2023/09/09 11:43 [pubmed]
PHST- 2023/09/09 01:13 [entrez]
PHST- 2023/09/01 00:00 [pmc-release]
AID - ijms241713567 [pii]
AID - ijms-24-13567 [pii]
AID - 10.3390/ijms241713567 [doi]
PST - epublish
SO  - Int J Mol Sci. 2023 Sep 1;24(17):13567. doi: 10.3390/ijms241713567.