Available online at www.sciencedirect.com
ScienceDirect Neuromuscular Disorders 24 (2014) 1122 www.elsevier.com/locate/nmd
Letters to the Editor
Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: A novel gene related to nuclear envelopathies
Response (to Sewry and Goebel)
We have read with interest the report published online by Kayman-Kurekci et al. [1] on the identification of the TOR1AIP1 gene encoding the nuclear membrane proteinLAPB1 lamin as a cause of a muscular dystrophy. We congratulate them on this finding. The report, however, on the ultrastructural features of the nuclei we consider is misleading in relation to the figures shown. Fig. 3 shows nuclear changes that can be observed in several neuromuscular disorders and the specificity of their observations is not reported. In addition, the appearance of the material in Fig. 3D and E indicated as ‘naked DNA’ resembles lipofuscin, a non-specific residual material from lysosomal degradation that is frequently observed in muscle, particularly in adults. It is not clear why the material is considered ‘DNA’. Lipofuscin stains red with the technique for acid phosphatase (using naphthol AS-B1 phosphate substrate and pararosaniline) and is autofluorescent. It is important to know if lipofuscin was detected and how it was distinguished from the material illustrated. Similarly in Fig. 3C the area labelled as naked ‘DNA’ resembles a nucleus with a nuclear membrane. We feel this needs clarification to avoid misleading reference and future quotation of observations that need further investigation.
We thank Dr. Sewry and Dr. Goebel for their valuable comments. As mentioned in the Discussion section, first paragraph, the ultrastructural changes related with nucleus covered about 40–60% of the nuclei and no cytoplasmic alteration was detected. Although these features are consistent with laminopathies [1,2], it is true that such nuclear changes could be non-specific changes of the diseased muscle too. Regarding the resemblance of DNA changes to lipofuscin pigments, no autofluorescence was detected on the frozen sections under confocal laser microscope. Serial sections were stained for acid phosphatase and positive staining that could be compatible with lipofuscin was detected in some fibres. We agree that the presence of lipofuscin can be a common non-specific feature in some conditions, such as atrophied fibres and also normal muscle [1]. However, we believe that the ultrastructural changes observed in the patient’s muscle belong to the nucleus and its chromatin material. Particularly, in transmission electron microscope some alterations including extrusion of nucleoplasm into the sarcoplasm, chromatin leak, extranuclear ‘naked’ chromatin were similar to those reported in X-linked cases of Emery-Dreifuss muscular dystrophy [3]. We agree with the dictation error about Fig. 3(C), the arrow indicated the nucleus but was put at the end of the sentence.
Reference
References
[1] Kayman-Kurekci G et al. Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: A novel gene related to nuclear envelopathies. Neuromuscul Disord 2014;24:624–33.
[1] Dubowitz V, Sewry CA, Oldfors A. Muscle Biopsy: a practical approach. 4th ed. Saunders Ltd., 2013. [2] Sewry CA, Brown SC, Mercuri E, et al. Skeletal muscle pathology in autosomal dominant Emery-Dreifuss muscular dystrophy with lamin A/C mutations. Neuropathol Appl Neurobiol 2001;27:281–90. [3] Fidzian´ska A, Toniolo D, Hausmanowa-Petrusewicz I. Ultrastructural abnormality of sarcolemmal nuclei in Emery-Dreifuss muscular dystrophy (EDMD). J Neurol Sci 1998;159(1):88–93.
Caroline A. Sewry Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Sick Children and Institute of Child Health, London, UK E-mail address: [email protected] Hans H. Goebel Charite´ – Universita¨tsmedizin Berlin, Germany E-mail address: [email protected]
doi:10.1016/j.nmd.2014.07.007
G. Kayman-Kurekci P. Korkusuz ⇑ P. Dincer on behalf of the co-authors Faculty of Medicine, Hacettepe University, Ankara, Turkey ⇑ Corresponding author. E-mail address: [email protected] (P. Dincer) doi:10.1016/j.nmd.2014.08.001
ScienceDirect Neuromuscular Disorders 24 (2014) 1122 www.elsevier.com/locate/nmd
Letters to the Editor
Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: A novel gene related to nuclear envelopathies
Response (to Sewry and Goebel)
We have read with interest the report published online by Kayman-Kurekci et al. [1] on the identification of the TOR1AIP1 gene encoding the nuclear membrane proteinLAPB1 lamin as a cause of a muscular dystrophy. We congratulate them on this finding. The report, however, on the ultrastructural features of the nuclei we consider is misleading in relation to the figures shown. Fig. 3 shows nuclear changes that can be observed in several neuromuscular disorders and the specificity of their observations is not reported. In addition, the appearance of the material in Fig. 3D and E indicated as ‘naked DNA’ resembles lipofuscin, a non-specific residual material from lysosomal degradation that is frequently observed in muscle, particularly in adults. It is not clear why the material is considered ‘DNA’. Lipofuscin stains red with the technique for acid phosphatase (using naphthol AS-B1 phosphate substrate and pararosaniline) and is autofluorescent. It is important to know if lipofuscin was detected and how it was distinguished from the material illustrated. Similarly in Fig. 3C the area labelled as naked ‘DNA’ resembles a nucleus with a nuclear membrane. We feel this needs clarification to avoid misleading reference and future quotation of observations that need further investigation.
We thank Dr. Sewry and Dr. Goebel for their valuable comments. As mentioned in the Discussion section, first paragraph, the ultrastructural changes related with nucleus covered about 40–60% of the nuclei and no cytoplasmic alteration was detected. Although these features are consistent with laminopathies [1,2], it is true that such nuclear changes could be non-specific changes of the diseased muscle too. Regarding the resemblance of DNA changes to lipofuscin pigments, no autofluorescence was detected on the frozen sections under confocal laser microscope. Serial sections were stained for acid phosphatase and positive staining that could be compatible with lipofuscin was detected in some fibres. We agree that the presence of lipofuscin can be a common non-specific feature in some conditions, such as atrophied fibres and also normal muscle [1]. However, we believe that the ultrastructural changes observed in the patient’s muscle belong to the nucleus and its chromatin material. Particularly, in transmission electron microscope some alterations including extrusion of nucleoplasm into the sarcoplasm, chromatin leak, extranuclear ‘naked’ chromatin were similar to those reported in X-linked cases of Emery-Dreifuss muscular dystrophy [3]. We agree with the dictation error about Fig. 3(C), the arrow indicated the nucleus but was put at the end of the sentence.
Reference
References
[1] Kayman-Kurekci G et al. Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: A novel gene related to nuclear envelopathies. Neuromuscul Disord 2014;24:624–33.
[1] Dubowitz V, Sewry CA, Oldfors A. Muscle Biopsy: a practical approach. 4th ed. Saunders Ltd., 2013. [2] Sewry CA, Brown SC, Mercuri E, et al. Skeletal muscle pathology in autosomal dominant Emery-Dreifuss muscular dystrophy with lamin A/C mutations. Neuropathol Appl Neurobiol 2001;27:281–90. [3] Fidzian´ska A, Toniolo D, Hausmanowa-Petrusewicz I. Ultrastructural abnormality of sarcolemmal nuclei in Emery-Dreifuss muscular dystrophy (EDMD). J Neurol Sci 1998;159(1):88–93.
Caroline A. Sewry Dubowitz Neuromuscular Centre, Great Ormond Street Hospital for Sick Children and Institute of Child Health, London, UK E-mail address: [email protected] Hans H. Goebel Charite´ – Universita¨tsmedizin Berlin, Germany E-mail address: [email protected]
doi:10.1016/j.nmd.2014.07.007
G. Kayman-Kurekci P. Korkusuz ⇑ P. Dincer on behalf of the co-authors Faculty of Medicine, Hacettepe University, Ankara, Turkey ⇑ Corresponding author. E-mail address: [email protected] (P. Dincer) doi:10.1016/j.nmd.2014.08.001
