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Domellöf, Fatima Pedrosa
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Publications (10 of 61) Show all publications
Rodríguez, M. A., Sandgren Hochhard, K., Vicente, A., Liu, J.-X. & Domellöf, F. P. (2019). Gene expression profile of extraocular muscles following resection strabismus surgery. Experimental Eye Research, 182, 182-193
Open this publication in new window or tab >>Gene expression profile of extraocular muscles following resection strabismus surgery
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2019 (English)In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 182, p. 182-193Article in journal (Refereed) Published
Abstract [en]

This paper aims to identify key biological processes triggered by resection surgery in the extraocular muscles (EOMs) of a rabbit model of strabismus surgery by studying changes in gene expression. Resection surgery was performed in the superior rectus of 16 rabbits and a group of non-operated rabbits served as control. Muscle samples were collected from groups of four animals 1, 2, 4 and 6 weeks after surgery and processed for RNA-sequencing and immunohistochemistry. We identified a total of 164; 136; 64 and 12 differentially expressed genes 1, 2, 4 and 6 weeks after surgery. Gene Ontology enrichment analysis revealed that differentially expressed genes were involved in biological pathways related to metabolism, response to stimulus mainly related with regulation of immune response, cell cycle and extracellular matrix. A complementary pathway analysis and network analysis performed with Ingenuity Pathway Analysis tool corroborated and completed these findings. Collagen I, fibronectin and versican, evaluated by immunofluorescence, showed that changes at the gene expression level resulted in variation at the protein level. Tenascin-C staining in resected muscles demonstrated the formation of new tendon and myotendinous junctions. These data provide new insights about the biological response of the EOMs to resection surgery and may form the basis for future strategies to improve the outcome of strabismus surgery.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Extraocular muscles, Strabismus, Gene expression, Resection surgery
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-159869 (URN)10.1016/j.exer.2019.03.022 (DOI)000468258300021 ()30953624 (PubMedID)
Funder
Swedish Research Council, 2018-02401Västerbotten County Council
Available from: 2019-06-10 Created: 2019-06-10 Last updated: 2019-06-10Bibliographically approved
Chandra, N., Liu, Y., Liu, J.-X., Frängsmyr, L., Wu, N., Silva, L. M., . . . Arnberg, N. (2019). Sulfated Glycosaminoglycans as Viral Decoy Receptors for Human Adenovirus Type 37. Viruses, 11(3), Article ID E247.
Open this publication in new window or tab >>Sulfated Glycosaminoglycans as Viral Decoy Receptors for Human Adenovirus Type 37
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2019 (English)In: Viruses, ISSN 1999-4915, E-ISSN 1999-4915, Vol. 11, no 3, article id E247Article in journal (Refereed) Published
Abstract [en]

Glycans on plasma membranes and in secretions play important roles in infection by many viruses. Species D human adenovirus type 37 (HAdV-D37) is a major cause of epidemic keratoconjunctivitis (EKC) and infects target cells by interacting with sialic acid (SA)-containing glycans via the fiber knob domain of the viral fiber protein. HAdV-D37 also interacts with sulfated glycosaminoglycans (GAGs), but the outcome of this interaction remains unknown. Here, we investigated the molecular requirements of HAdV-D37 fiber knob:GAG interactions using a GAG microarray and demonstrated that fiber knob interacts with a broad range of sulfated GAGs. These interactions were corroborated in cell-based assays and by surface plasmon resonance analysis. Removal of heparan sulfate (HS) and sulfate groups from human corneal epithelial (HCE) cells by heparinase III and sodium chlorate treatments, respectively, reduced HAdV-D37 binding to cells. Remarkably, removal of HS by heparinase III enhanced the virus infection. Our results suggest that interaction of HAdV-D37 with sulfated GAGs in secretions and on plasma membranes prevents/delays the virus binding to SA-containing receptors and inhibits subsequent infection. We also found abundant HS in the basement membrane of the human corneal epithelium, which may act as a barrier to sub-epithelial infection. Collectively, our findings provide novel insights into the role of GAGs as viral decoy receptors and highlight the therapeutic potential of GAGs and/or GAG-mimetics in HAdV-D37 infection.

Place, publisher, year, edition, pages
MDPI, 2019
Keywords
adenovirus, antiviral drugs, cellular receptor, decoy receptor, epidemic keratoconjunctivitis, glycosaminoglycan, tropism
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-158515 (URN)10.3390/v11030247 (DOI)000464389700003 ()30871026 (PubMedID)
Funder
Knut and Alice Wallenberg Foundation, KAW 2013.0019Swedish Research Council, 2018-02401Västerbotten County CouncilWellcome trust, 099197MA
Available from: 2019-04-29 Created: 2019-04-29 Last updated: 2019-08-28Bibliographically approved
Liu, J.-X. & Pedrosa-Domellöf, F. (2018). A novel type of multiterminal motor endplate in human extraocular muscles. Investigative Ophthalmology and Visual Science, 59(1), 539-548
Open this publication in new window or tab >>A novel type of multiterminal motor endplate in human extraocular muscles
2018 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 1, p. 539-548Article in journal (Refereed) Published
Abstract [en]

Purpose: To investigate the relation between type of motor endplate, acetylcholine receptor (AChR) subunit composition, and fiber types in human extraocular muscles (EOMs).

Methods: EOM samples collected from subjects aged 34 to 82 years were serially sectioned and processed for immunohistochemistry, with specific antibodies against different myosin heavy chain (MyHC) isoforms, neurofilament, synaptophysin, and adult epsilon (ε) and fetal gamma (γ) AChR subunits as well as α-bungarotoxin.

Results: A novel type of motor endplate consisting of large, multiterminal en plaque endings was found in human EOMs, in addition to the previously well-described single en plaque and multiple en grappe endplates. Such novel endplates were abundant but exclusively observed in myofibers lacking MyHC slow and fast IIa but containing MyHC extraocular (MyHCeom), isoforms. Multiple en grappe endings were found only in myofibers containing MyHC slow-tonic isoform and contained fetal γ AChR subunit. Adult ε and fetal γ AChR subunits, alone or combined, were found in the multiterminal endplates. Distinct AChR subunits were present in adjacent motor endplates of a given myofiber containing MyHCeom.

Conclusions: Human EOMs have a more complex innervation pattern than previously described, comprising also a novel type of multiterminal motor endplate present in myofibers containing MyHCeom. The heterogeneity in AChR subunit composition in a given myofiber suggests the possible presence of polyneuronal innervation in human EOMs.

Place, publisher, year, edition, pages
Rockville: The Association for Research in Vision and Ophthalmology, 2018
Keywords
extraocular muscles, motor endplate, multiterminal motor endplate, en grappe, en plaque, polyneuronal innervation, myosin heavy chain, acetylcholine receptor subunit
National Category
Cell and Molecular Biology Ophthalmology
Research subject
Medical Cell Biology
Identifiers
urn:nbn:se:umu:diva-145396 (URN)10.1167/iovs.17-22554 (DOI)000425855900064 ()29372252 (PubMedID)
Available from: 2018-03-01 Created: 2018-03-01 Last updated: 2018-06-09Bibliographically approved
Vicente, A., Byström, B. & Domellöf, F. P. (2018). Altered Signaling Pathways in Aniridia-Related Keratopathy. Investigative Ophthalmology and Visual Science, 59(13), 5531-5541
Open this publication in new window or tab >>Altered Signaling Pathways in Aniridia-Related Keratopathy
2018 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 13, p. 5531-5541Article in journal (Refereed) Published
Abstract [en]

PURPOSE. To study the Notch1, Wnt/beta-catenin, sonic hedgehog (SHH), and mammalian target of rapamycin (mTOR) cell signaling pathways in naive and surgically treated corneas of aniridia cases with advanced aniridia-related keratopathy (ARK).

METHODS. Two naive corneal buttons from patients with advanced ARK submitted to penetrating keratoplasty for the first time, one corneal button from an ARK patient that had undergone a keratolimbal allograft (KLAL), two corneal buttons from ARK patients who had previously undergone centered or decentered transplantation, and two adult healthy control corneas were processed for immunohistochemistry in this descriptive study. Antibodies specific against elements of the Notch1 (Notch1; Dlk1; Numb), Wnt/beta-catenin (Wnt5a; Wnt7a; beta-catenin), SHH (glioma-associated oncogene homolog [Gli1]; Hes1), and mTOR (mTOR1; ribosomal protein S6 [rpS6]) signaling pathways were used as well as antibodies against PAX6 and keratin 13 (Krt13).

RESULTS. All ARK corneas presented signs of conjunctivalization and analogous signaling pathway changes in the subepithelial pannus and epithelium, with decreased detection of the Notch1 signaling pathway and an increased presence of the Notch1 inhibitors Numb and Dlk1. Increased detections of Wnt/beta-catenin (enhanced presence of Wnt5a, Wnt7a, and beta-catenin), SHH (detection of Gli1 and Hes1), and mTOR (identification of mTOR and rpS6) signaling pathways were found in the subepithelial pannus and epithelium of all ARK corneas, when compared with normal controls.

CONCLUSIONS. The similarity in pathway alterations found in all ARK corneas, irrespective of limbal stem cell transplantation, further supports the discussion on the role of host-specific factors and limbal stem cell deficiency in ARK.

Place, publisher, year, edition, pages
The Association for Research in Vision and Ophthalmology, 2018
Keywords
aniridia-related keratopathy, signaling pathways, keratoplasty, keratolimbal allograft, limbal stem cell deficiency, PAX6, sonic hedgehog, mTOR, Wnt, Notch1
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-155119 (URN)10.1167/iovs.18-25175 (DOI)000452609300004 ()30480741 (PubMedID)
Funder
Swedish Research Council, 2015-02438Västerbotten County Council
Available from: 2019-01-08 Created: 2019-01-08 Last updated: 2019-10-18Bibliographically approved
Vicente, A., Byström, B., Lindström, M., Stenevi, U. & Pedrosa Domellöf, F. (2018). Aniridia-related keratopathy: structural changes in naïve and transplanted corneal buttons. PLoS ONE, 13(6), Article ID e0198822.
Open this publication in new window or tab >>Aniridia-related keratopathy: structural changes in naïve and transplanted corneal buttons
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 6, article id e0198822Article in journal (Refereed) Published
Abstract [en]

Background: To study structural changes in naive and surgically treated corneas of aniridia patients with advanced aniridia-related keratopathy (ARK).

Methods and findings: Two naive corneal buttons from patients with advanced ARK submitted to penetrating keratoplasty for the first time, one corneal button from an ARK patient that had undergone a keratolimbal allograft (KLAL), two corneal buttons from ARK patients who had previously undergone centered or decentered transplantation and were now retransplanted and two adult healthy donor control corneas were processed for immunohistochemistry. Antibodies against extracellular matrix components in the stroma and in the epithelial basement membrane (collagen I and IV, collagen receptor alpha 11 integrin and laminin alpha 3 chain), markers of fibrosis, wound healing and vascularization (fibronectin, tenascin-C, vimentin, alpha-SMA and caveolin-1), cell division (Ki-67) and macrophages (CD68) were used. Naive ARK, KLAL ARK corneas and transplanted corneal buttons presented similar histopathological changes with irregular epithelium and disruption or absence of epithelial basal membrane. There was a loss of the orderly pattern of collagen lamellae and absence of collagen I in all ARK corneas. Vascularization was revealed by the presence of caveolin-1 and collagen IV in the pannus of all ARK aniridia corneas. The changes observed in decentered and centered transplants were analogous.

Conclusions: Given the similar pathological features of all cases, conditions inherent to the host seem to play an important role on the pathophysiology of the ARK in the long run.

Place, publisher, year, edition, pages
Public Library of Science, 2018
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-150386 (URN)10.1371/journal.pone.0198822 (DOI)000434786600055 ()29889891 (PubMedID)2-s2.0-85048312123 (Scopus ID)
Available from: 2018-08-06 Created: 2018-08-06 Last updated: 2019-10-18Bibliographically approved
Crippa, S. V., Domellöf, F. P. & Kawasaki, A. (2018). Chromatic pupillometry in children. Frontiers in Neurology, 9, Article ID 669.
Open this publication in new window or tab >>Chromatic pupillometry in children
2018 (English)In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 9, article id 669Article in journal (Refereed) Published
Abstract [en]

Chromatic pupillometry is a technique that is increasingly used to assess retinal disorders. As age may be one of the various factors which can influence the pupillary light reaction, this study aimed to evaluate the pupil responses to colored light stimuli in the pediatric population. Fifty-three children with normal vision and without any history of ocular disorders were tested with a portable pupillometer. Four test sequences were used: five dim blue (470 nm) stimuli presented in half log steps ranging from -3.15 to -1.15 log cd/m(2) after 3 min of dark adaptation, five red (622 nm) stimuli of -1.15, -0.7, -0.15, 0.3, and 0.85 log cd/m(2) after 1 min light adaptation, one bright blue stimulus of 2.2 log cd/m(2) and one bright red of 2 log cd/m(2). The results were grouped by age: a younger group included 27 children aged from 3 to 10 years old and an older group included 26 from 10 and 1 month to 18 years old. The younger group had a smaller pupil diameter after dark adaptation compared with the older group. A linear regression defining the photopic threshold showed that younger subjects had a higher threshold, e.g., needed a brighter red stimulus to evoke a threshold pupil response comparable that of subjects. Age thus seems to influence outer retinal sensitivity at least as evaluated by the pupillary photopic threshold intensity. The post-illumination pupillary reaction was used as a marker of intrinsic melanopsin activity and did not show any difference between the two age groups.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2018
Keywords
pupil, chromatic pupillometry, children, pupillary light reaction, growth
National Category
Ophthalmology Neurology
Identifiers
urn:nbn:se:umu:diva-151389 (URN)10.3389/fneur.2018.00669 (DOI)000441937500001 ()30174642 (PubMedID)
Available from: 2018-09-06 Created: 2018-09-06 Last updated: 2018-09-06Bibliographically approved
McLoon, L. K., Vicente, A., Fitzpatrick, K. R., Lindström, M. & Pedrosa Domellöf, F. (2018). Composition, architecture, and functional implications of the connective tissue network of the extraocular muscles. Investigative Ophthalmology and Visual Science, 59(1), 322-329
Open this publication in new window or tab >>Composition, architecture, and functional implications of the connective tissue network of the extraocular muscles
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2018 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 1, p. 322-329Article in journal (Refereed) Published
Abstract [en]

Purpose: We examined the pattern and extent of connective tissue distribution in the extraocular muscles (EOMs) and determined the ability of the interconnected connective tissues to disseminate force laterally.

Methods: Human EOMs were examined for collagens I, III, IV, and VI; fibronectin; laminin; and elastin using immunohistochemistry. Connective tissue distribution was examined with scanning electron microscopy. Rabbit EOMs were examined for levels of force transmission longitudinally and transversely using in vitro force assessment.

Results: Collagens I, III, and VI localized to the endomysium, perimysium, and epimysium. Collagen IV, fibronectin, and laminin localized to the basal lamina surrounding all myofibers. All collagens localized similarly in the orbital and global layers throughout the muscle length. Elastin had the most irregular pattern and ran longitudinally and circumferentially throughout the length of all EOMs. Scanning electron microscopy showed these elements to be extensively interconnected, from endomysium through the perimysium to the epimysium surrounding the whole muscle. In vitro physiology demonstrated force generation in the lateral dimension, presumably through myofascial transmission, which was always proportional to the force generated in the longitudinally oriented muscles.

Conclusions: A striking connective tissue matrix interconnects all the myofibers and extends, via perimysial connections, to the epimysium. These interconnections are significant and allow measurable force transmission laterally as well as longitudinally, suggesting that they may contribute to the nonlinear force summation seen in motor unit recording studies. This provides strong evidence that separate compartmental movements are unlikely as no region is independent of the rest of the muscle.

Place, publisher, year, edition, pages
Rockville: The Association for Research in Vision and Ophthalmology, 2018
Keywords
extraocular muscles, connective tissue, collagen, muscle force, scanning electron microscopy, perimysium, epimysium
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-146324 (URN)10.1167/iovs.17-23003 (DOI)000425855900038 ()29346490 (PubMedID)
Available from: 2018-04-05 Created: 2018-04-05 Last updated: 2018-06-09Bibliographically approved
Vicente, A., Pedrosa Domellöf, F. & Byström, B. (2018). Exophiala phaeomuriformis keratitis in a subarctic climate region: a case report. Acta Ophthalmologica, 96, 425-428
Open this publication in new window or tab >>Exophiala phaeomuriformis keratitis in a subarctic climate region: a case report
2018 (English)In: Acta Ophthalmologica, ISSN 1755-375X, E-ISSN 1755-3768, Vol. 96, p. 425-428Article in journal (Refereed) Published
Abstract [en]

PURPOSE: To report a case of Exophiala phaeomuriformis mycotic keratitis in a patient from a subarctic climate region. Dematiaceous fungi (black yeasts) have been gaining importance as corneal keratitis and ulcer causative agents in certain regions, but no cases have been described in Scandinavia.

METHODS: Case report of a patient with a persistent corneal erosion that eventually presented a brown-pigmented infiltrate. The patient had a history of several months of topical therapy comprising medication for glaucoma, corticosteroids and antibiotics. A therapeutic contact lens was used, and amniotic membrane transplantation was performed before the development of the pigmented infiltrate.

RESULTS: Exophiala phaeomuriformis was identified on the microbiological cultures from the surgically obtained infiltrate scrapes. The patient responded to topical amphotericin and fluconazole, the erosion was cured and a stromal scar subsided. During follow-up, sequential slit-lamp images and anterior segment optical coherence tomography (OCT) scans were obtained.

CONCLUSION: This is the first described case of keratitis caused by E. phaeomuriformis in a subarctic region, the first in Europe and, to our knowledge, the second reported case in the literature. It is important to remember that superficial corneal brown-pigmented infiltrates should raise the suspicion of an unusual fungal infection even in this climate. This is particularly important in patients with ocular surface disease treated with steroids and antibiotics for a long time.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
Exophiala phaeomuriformis, amniotic membrane transplantation, anterior segment OCT, mycotic keratitis
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-145254 (URN)10.1111/aos.13624 (DOI)000439737000042 ()29193858 (PubMedID)2-s2.0-85036520949 (Scopus ID)
Available from: 2018-02-26 Created: 2018-02-26 Last updated: 2018-11-01Bibliographically approved
Byström, B., Vicente, A. & Domellöf, F. P. (2018). Notch1 Signaling Pathway in Aniridia- Related Keratopathy, Normal Fetal and Adult Human Corneas. Paper presented at Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), APR 29-MAY 03, 2018, Honolulu, HI. Investigative Ophthalmology and Visual Science, 59(9)
Open this publication in new window or tab >>Notch1 Signaling Pathway in Aniridia- Related Keratopathy, Normal Fetal and Adult Human Corneas
2018 (English)In: Investigative Ophthalmology and Visual Science, ISSN 0146-0404, E-ISSN 1552-5783, Vol. 59, no 9Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Purpose : Notch1 is suggested to play an important role during tissue development and in differentiation of the corneal epithelial cells whereas its inhibitors Dlk1 and Numb keep these cells in an immature status. Our purpose was to evaluate the presence of these factors in aniridia-related keratopathy (ARK) and in normal fetal and adult human corneas.

Methods : Two human fetal corneas, 10 and 20 weeks of gestation, two naïve corneal buttons from patients with advanced ARK, three corneal buttons from patients with ARK undergoing re-transplantation, as well as two adult healthy control corneas were processed for immunohistochemistry using antibodies against Notch1, Dlk1 and Numb.

Results : Identical staining patterns were found for Notch1 in normal adult and fetal corneas, with staining around the basal epithelial cells and in a few streaks in the stroma. In ARK corneas, Notch1 was not detected in the pannus of the stroma. On the contrary, the pannus in ARK was labeled with antibodies against Dlk1. Dlk1 was also abundant in the epithelium and in the stroma of fetal corneas but was absent from the stroma of normal adult corneas. Numb was present in the adult normal corneas and in addition labeled the ARK and fetal corneas in a pattern resembling that of Dlk1.

Conclusions : The lack of Notch1 together with abundant Dlk1 and Numb, suggest a disturbed balance between these important factors in ARK, likely to hamper differentiation of the progenitor cell population and to be important for the pathophysiology of ARK.

Place, publisher, year, edition, pages
The Association for Research in Vision and Ophthalmology, Inc., 2018
National Category
Ophthalmology
Identifiers
urn:nbn:se:umu:diva-152276 (URN)000442912506241 ()
Conference
Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO), APR 29-MAY 03, 2018, Honolulu, HI
Funder
Swedish Research Council, K2012-63x-20399-06-3Västerbotten County Council
Available from: 2018-10-02 Created: 2018-10-02 Last updated: 2018-10-02Bibliographically approved
Nilipour, Y., Nafissi, S., Tjust, A. E., Ravenscroft, G., Hossein Nejad Nedai, H., Taylor, R. L., . . . Tajsharghi, H. (2018). Ryanodine receptor type 3 (RYR3) as a novel gene associated with a myopathy with nemaline bodies. European Journal of Neurology, 25(6), 841-847
Open this publication in new window or tab >>Ryanodine receptor type 3 (RYR3) as a novel gene associated with a myopathy with nemaline bodies
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2018 (English)In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 25, no 6, p. 841-847Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND PURPOSE: Nemaline myopathy (NEM) has been associated with mutations in 12 genes to date. However, for some patients diagnosed with NEM, definitive mutations are not identified in the known genes, suggesting that there are other genes involved. This study describes compound heterozygosity for rare variants in ryanodine receptor type 3 (RYR3) gene in one such patient.

METHODS AND RESULTS: Clinical examination of the patient at 22 years of age revealed a long narrow face, high arched palate and bilateral facial weakness. She had proximal weakness in all four limbs, mild scapular winging but no scoliosis. Muscle biopsy revealed wide variation in fibre size with type 1 fibre predominance and atrophy. Abundant nemaline bodies were located in perinuclear and subsarcolemmal areas, and within the cytoplasm. No likely pathogenic mutations in known NEM genes were identified. Copy number variation in known NEM genes was excluded by NEM-targeted comparative genomic hybridization array. Next-generation sequencing revealed compound heterozygous missense variants in the RYR3 gene. RYR3 transcripts are expressed in human fetal and adult skeletal muscle as well as in human brain and cauda equina samples. Immunofluorescence of human skeletal muscle revealed a 'single-row' appearance of RYR3, interspersed between the 'double rows' of ryanodine receptor type 1 (RYR1) at each A-I junction.

CONCLUSION: The results suggest that variants in RYR3 may cause a recessive muscle disease with pathological features including nemaline bodies. We characterize the expression pattern of RYR3 in human skeletal muscle and brain, and the subcellular localization of RYR1 and RYR3 in human skeletal muscle.

Keywords
RYR3, intracellular Ca2+ channels, nemaline myopathy, ryanodine receptors
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-146323 (URN)10.1111/ene.13607 (DOI)000431989200012 ()29498452 (PubMedID)
Available from: 2018-04-05 Created: 2018-04-05 Last updated: 2019-04-08Bibliographically approved
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