Muscular and Molecular Pathology Associated with SPATA5 Deficiency in a Child with EHLMRS
Abstract
:1. Introduction
2. Results
2.1. Clinical Findings
2.2. Genetic Findings
2.3. Muscle Biopsy Findings
2.4. Proteomic Profiling
3. Discussion
4. Materials and Methods
4.1. Exome-Sequencing
4.2. Histology and Enzyme Histochemistry, Immunohistology
4.3. Human Muscle Preparation for Mass Spectrometry
4.4. DIA-LC-MS/MS Analysis
4.5. Analysis of DIA Data
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data availability statement
Acknowledgments
Conflicts of Interest
References
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UniProt Entry | Gene Name | Patient vs. Control | p-Value |
---|---|---|---|
HMCS2_HUMAN | HMGCS2 | 6.67 | 0.000 |
SPEB_HUMAN | AGMAT | 2.46 | 0.000 |
THIM_HUMAN | ACAA2 | 2.38 | 0.000 |
KAD3_HUMAN | AK3 | 1.98 | 0.001 |
ATPD_HUMAN | ATP5F1D | 1.98 | 0.003 |
ETFB_HUMAN | ETFB | 1.95 | 0.000 |
ECHA_HUMAN | HADHA | 1.91 | 0.000 |
NDUB6_HUMAN | NDUFB6 | 1.90 | 0.003 |
COX5B_HUMAN | COX5B | 0.54 | 0.008 |
CMC1_HUMAN | SLC25A12 | 0.53 | 0.011 |
ATP5J_HUMAN | ATP5J | 0.52 | 0.009 |
COX1_HUMAN | MT-CO1 | 0.50 | 0.026 |
KAD2_HUMAN | AK2 | 0.50 | 0.008 |
CQ10A_HUMAN | COQ10A | 0.49 | 0.034 |
HXK1_HUMAN | HK1 | 0.31 | 0.000 |
Protein | Localization | Gene Name | p-Value 3 | Associated Disease (#OMIM) |
---|---|---|---|---|
PURA1_HUMAN 1 | Cytoplasm | ADSSL1 | 0.000 | # 617030 MYOPATHY, DISTAL, 5; MPD5 |
LAMA2_HUMAN 1 | Extracellular, basement membrane | LAMA2 | 0.013 | # 607855 MUSCULAR DYSTROPHY, CONGENITAL MEROSIN-DEFICIENT, 1A; MDC1A |
# 618138 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 23; LGMDR23 | ||||
ETFB_HUMAN 1 | Mitochondrion matrix | ETFB | 0.000 | # 231680 GLUTARIC ACIDEMIA IIB, INCLUDED; GA2B, INCLUDED ETFB DEFICIENCY, INCLUDED |
ECHA_HUMAN 1 | Mitochondrion inner membrane | HADHA | 0.000 | # 609015 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY; MTPD |
# 609016 LONG-CHAIN 3-HYDROXYACYL-CoA DEHYDROGENASE DEFICIENCY | ||||
# 231680 MULTIPLE ACYL-CoA DEHYDROGENASE DEFICIENCY; MADD | ||||
CMC1_HUMAN 2 | Mitochondrion inner membrane; multi-pass membrane protein | SLC25A12 | 0.011 | # 612949 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 39; DEE39 |
TELT_HUMAN 2 | Sarcomere | TCAP | 0.004 | # 607487 CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 25; CMH25 # 601954 MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 7; LGMDR7 |
COX1_HUMAN 2 | Mitochondrion inner membrane; multi-pass membrane protein | MT-CO1 | 0.026 | # 535000 LEBER OPTIC ATROPHY |
# 220110 MITOCHONDRIAL COMPLEX IV DEFICIENCY, NUCLEAR TYPE 1; MC4DN1 | ||||
# 550500 MYOGLOBINURIA, RECURRENT | ||||
# 500008 DEAFNESS, NONSYNDROMIC SENSORINEURAL, MITOCHONDRIAL | ||||
# 114500 COLORECTAL CANCER; CRC | ||||
HSPB8_HUMAN 2 | Nucleus; cytoplasm | HSPB8 | 0.039 | # 158590 NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE IIA; HMN2A |
# 608673 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2L; CMT2L | ||||
SPRE_HUMAN 2 | Cytoplasm | SPR | 0.014 | # 612716 DYSTONIA, DOPA-RESPONSIVE, DUE TO SEPIAPTERIN REDUCTASE DEFICIENCY |
HEM2_HUMAN 2 | Cytosol; extracellular exosome; extracellular region; nucleus; ficolin-1-rich granule lumen; secretory granule lumen | ALAD | 0.031 | # 612740 PORPHYRIA, ACUTE HEPATIC |
CAH2_HUMAN 2 | Cell membrane; cytoplasm | CA2 | 0.050 | # 259730 OSTEOPETROSIS, AUTOSOMAL RECESSIVE 3; OPTB3 |
CATD_HUMAN 2 | Lysosome; extracellular space; melanosome | CTSD | 0.003 | # 610127 CEROID LIPOFUSCINOSIS, NEURONAL, 10; CLN10 |
LDHA_HUMAN 2 | Cytoplasm | LDHA | 0.009 | # 612933 GLYCOGEN STORAGE DISEASE XI; GSD11 |
HXK1_HUMAN 2 | Cytosol; mitochondrion outer membrane; peripheral membrane protein | HK1 | 0.000 | # 235700 HEMOLYTIC ANEMIA, NONSPHEROCYTIC, DUE TO HEXOKINASE DEFICIENCY |
# 605285 NEUROPATHY, HEREDITARY MOTOR AND SENSORY, RUSSE TYPE; HMSNR | ||||
# 617460 RETINITIS PIGMENTOSA 79; RP79 | ||||
# 618547 NEURODEVELOPMENTAL DISORDER WITH VISUAL DEFECTS AND BRAIN ANOMALIES; NEDVIBA | ||||
SMPX_HUMAN 2 | Nucleus; costamere; M band—muscle tendon junction | SMPX | 0.036 | # 300066 DEAFNESS, X-LINKED 4; DFNX4 |
VATA_HUMAN 2 | Cytoplasm | ATP6V1A | 0.006 | # 617403 CUTIS LAXA, AUTOSOMAL RECESSIVE, TYPE IID; ARCL2D |
# 618012 DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 93; DEE93 | ||||
PRPS1_HUMAN 2 | Cytosol; cytoplasm—ribose phosphate diphosphokinase complex | PRPS1 | 0.040 | # 300661 PHOSPHORIBOSYLPYROPHOSPHATE SYNTHETASE SUPERACTIVITY |
# 311070 CHARCOT-MARIE-TOOTH DISEASE, X-LINKED RECESSIVE, 5; CMTX5 | ||||
# 301835 ARTS SYNDROME; ARTS | ||||
# 304500 DEAFNESS, X-LINKED 1; DFNX1 | ||||
CO5A1_HUMAN 2 | Extracellular matrix | COL5A1 | 0.007 | # 130000 EHLERS-DANLOS SYNDROME, CLASSIC TYPE, 1; EDSCL1 |
ACY1_HUMAN 2 | Cytoplasm | ACY1 | 0.002 | # 609924 AMINOACYLASE 1 DEFICIENCY; ACY1D |
Primary Antibody, Clone | Company | Number | Dilution |
---|---|---|---|
Caveolin 3, 26/Caveolin3 | BD Transduction Laboratories | 610420 | 1:500 |
Dystrophin 1, Dy4/6d3 | Novocastra/Leica | NCL-DYS1 | 1:2 |
Dystrophin 2, Dy8/6c5 | Novocastra/Leica | NCL-DYS2 | 1:10 |
Dystrophin 3, Dy10/12B2 | Novocastra/Leica | NCL-DYS3 | 1:10 |
α-Dystroglycan, VIA4-1 | Merck/Upstate | #05-298 | 1:15 |
β-Dystroglycan, 43DAG1/8D5 | Novocastra/Leica | NCL-b-DG | 1:10 |
α-Sarcoglycan, Ad1/20A6 | Novocastra/Leica | NCL-a-SARC | 1:50 |
β-Sarcoglycan, βSarc/5B1 | Novocastra/Leica | NCL-b-SARC | 1:50 |
γ-Sarcoglycan, 35DAG/21B5 | Novocastra/Leica | NCL-g-SARC | 1:50 |
δ-Sarcoglycan, 35DAG/21B5 | Novocastra/Leica | NCL-d-SARC | 1:10 |
Laminin α2 C-term., 5H2 | Merck/Chemicon | MAB1922 | 1:500 |
Emerin, 4G5 | Novocastra/Leica | NCL-EMERIN | 1:20 |
Dysferlin, Hamlet 1 | Novocastra/Leica | NCL-HAMLET | 1:5 |
Collagen 6, VI-26 | Merck/Chemicon | MAB3303 | 1:100 |
Collagen 6, 3C4 | Merck/Chemicon | MAB1944 | 1:200 |
Collagen 4, polyclonal | Cedarline | CL50411AP | 1:100 |
Laminin α5, 4C7 | Merck/Chemicon | MAB1924 | 1:500 |
DRP 2 (Utrophin), DRP3/20C5 | Novocastra/Leica | NCL-DRP2 | 1:5 |
Neonatal Myosin, WB-MHCn | Novocastra/Leica | NCL-MHCn | 1:5 |
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Braun, F.; Hentschel, A.; Sickmann, A.; Marteau, T.; Hertel, S.; Förster, F.; Prokisch, H.; Wagner, M.; Wortmann, S.; Della Marina, A.; et al. Muscular and Molecular Pathology Associated with SPATA5 Deficiency in a Child with EHLMRS. Int. J. Mol. Sci. 2021, 22, 7835. https://doi.org/10.3390/ijms22157835
Braun F, Hentschel A, Sickmann A, Marteau T, Hertel S, Förster F, Prokisch H, Wagner M, Wortmann S, Della Marina A, et al. Muscular and Molecular Pathology Associated with SPATA5 Deficiency in a Child with EHLMRS. International Journal of Molecular Sciences. 2021; 22(15):7835. https://doi.org/10.3390/ijms22157835
Chicago/Turabian StyleBraun, Frederik, Andreas Hentschel, Albert Sickmann, Theodore Marteau, Swantje Hertel, Fabian Förster, Holger Prokisch, Matias Wagner, Saskia Wortmann, Adela Della Marina, and et al. 2021. "Muscular and Molecular Pathology Associated with SPATA5 Deficiency in a Child with EHLMRS" International Journal of Molecular Sciences 22, no. 15: 7835. https://doi.org/10.3390/ijms22157835
APA StyleBraun, F., Hentschel, A., Sickmann, A., Marteau, T., Hertel, S., Förster, F., Prokisch, H., Wagner, M., Wortmann, S., Della Marina, A., Kölbel, H., Roos, A., & Schara-Schmidt, U. (2021). Muscular and Molecular Pathology Associated with SPATA5 Deficiency in a Child with EHLMRS. International Journal of Molecular Sciences, 22(15), 7835. https://doi.org/10.3390/ijms22157835