We have investigated the frequency of deletions in the dystrophin gene in 108 unrelated Duchenne and Becker muscular dystrophy (DMD/BMD) patients from southern Italy (DMD, n. 47; BMD, n. 61) and identified 89 deletions. The de novo mutation rate (about 35%), and the preferentially maternal origin of deletional mutations, analysed in families in which the maternal grandparents were available or their haplotypes could be unequivocally reconstructed, are in agreement with data reported for other populations. The correlation between BMD phenotype and type of deletion suggests that, at the distal rod domain region, the deletion size may not be as crucial as the particular combination of missing exons. In fact, we provide immunohistochemical and clinical evidence that the in-frame deletion of the hinge III region at the distal rod domain results in a milder phenotype as compared with shorter deletions that do not include the hinge III region. Our data obtained in BMD patients confirm the inferences coming from minigene transfection experiments in mdx mice (Harper et al 2002 Nat. Med.; 8, 253-261) and give an important contribution to the design of constructs for gene therapy approaches.

Analysis of dystrophin gene deletions correlates the hinge III region of the protein with the disease severity. Ann. Hum Genet. 69: 253-9 / Carsana, Antonella; Frisso, Giulia; Tremolaterra, M. R.; Lanzillo, Roberta; Vitale, D. F.; Santoro, Lucio; Salvatore, Francesco. - In: ANNALS OF HUMAN GENETICS. - ISSN 0003-4800. - STAMPA. - 69:Pt 3(2005), pp. 253-259. [10.1046/J.1469-1809.2005.00160.x]

Analysis of dystrophin gene deletions correlates the hinge III region of the protein with the disease severity. Ann. Hum Genet. 69: 253-9.

CARSANA, ANTONELLA;LANZILLO, ROBERTA;SANTORO, LUCIO;SALVATORE, FRANCESCO
2005

Abstract

We have investigated the frequency of deletions in the dystrophin gene in 108 unrelated Duchenne and Becker muscular dystrophy (DMD/BMD) patients from southern Italy (DMD, n. 47; BMD, n. 61) and identified 89 deletions. The de novo mutation rate (about 35%), and the preferentially maternal origin of deletional mutations, analysed in families in which the maternal grandparents were available or their haplotypes could be unequivocally reconstructed, are in agreement with data reported for other populations. The correlation between BMD phenotype and type of deletion suggests that, at the distal rod domain region, the deletion size may not be as crucial as the particular combination of missing exons. In fact, we provide immunohistochemical and clinical evidence that the in-frame deletion of the hinge III region at the distal rod domain results in a milder phenotype as compared with shorter deletions that do not include the hinge III region. Our data obtained in BMD patients confirm the inferences coming from minigene transfection experiments in mdx mice (Harper et al 2002 Nat. Med.; 8, 253-261) and give an important contribution to the design of constructs for gene therapy approaches.
2005
Analysis of dystrophin gene deletions correlates the hinge III region of the protein with the disease severity. Ann. Hum Genet. 69: 253-9 / Carsana, Antonella; Frisso, Giulia; Tremolaterra, M. R.; Lanzillo, Roberta; Vitale, D. F.; Santoro, Lucio; Salvatore, Francesco. - In: ANNALS OF HUMAN GENETICS. - ISSN 0003-4800. - STAMPA. - 69:Pt 3(2005), pp. 253-259. [10.1046/J.1469-1809.2005.00160.x]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/333389
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