Patients with Duchenne muscular dystrophy are significantly shorter than those with Becker muscular dystrophy, with the higher incidence of short stature in Dp71 mutated subgroup

Matsumoto, Masaaki; Awano, Hiroyuki; Lee, Tomoko; Takeshima, Yasuhiro; Matsuo, Masafumi; Iijima, Kazumoto

doi:10.1016/j.nmd.2017.06.007

Cited by 22 publications

(19 citation statements)

References 33 publications

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“…About 7% of DMD patients are Dp116 deficient; thus, if Dp116 deficiency alone is directly responsible for the development of complications, the incidence of complications is about 7% [ 6 ]. A survey of complications in over 200 DMD patients found that the five most commonly reported conditions were cognitive deficits, constipation, anxiety problems, depression, and obesity [ 35 ].…”

Section: Clinical Findings Associated With Dp116mentioning

confidence: 99%

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Dystrophin Dp116: A yet to Be Investigated Product of the Duchenne Muscular Dystrophy Gene

Matsuo

Awano

Matsumoto

et al. 2017

Genes

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The Duchenne muscular dystrophy (DMD) gene is one of the largest genes in the human genome. The gene exhibits a complex arrangement of seven alternative promoters, which drive the expression of three full length and four shorter isoforms. Dp116, the second smallest product of the DMD gene, is a Schwann cell-specific isoform encoded by a transcript corresponding to DMD exons 56–79, starting from a promoter/exon S1 within intron 55. The physiological roles of Dp116 are poorly understood, because of its extensive homology with other isoforms and its expression in specific tissues. This review summarizes studies on Dp116, focusing on clinical findings and alternative activation of the upstream translation initiation codon that is predicted to produce Dp118.

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Section: Clinical Findings Associated With Dp116mentioning

confidence: 99%

“…Cardiac or respiratory complications are life-threatening. DMD may also be accompanied by non-muscle symptoms [ 1 ], including mental retardation [ 2 ], red–green color vision impairment [ 3 ], electroretinogram abnormalities [ 4 ] and short stature [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Dystrophin Dp116: A yet to Be Investigated Product of the Duchenne Muscular Dystrophy Gene

Matsuo

Awano

Matsumoto

et al. 2017

Genes

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“…However, the deletion of Xp22 as part of a contiguous gene deletion syndrome is only found in a minority of boys with DMD [ 28 ]. Two studies in DMD have identified that short stature is more common in boys with DMD with distal deletions suggesting a genotype effect on linear growth in DMD [ 1 , 29 ]. Both studies did not evaluate body segments.…”

Section: Discussionmentioning

confidence: 99%

“…Several observations point to the possibility that DMD, itself, may be associated with a growth disorder. Approximately, a quarter of boys with DMD are short prior to initiation of GC [ 1 – 3 ], and growth failure that pre-dates the initiation of GC therapy has been reported [ 4 ]. It is increasingly recognised that the majority of adolescent boys with DMD who continue on GC may have persistent hypogonadism.…”

Section: Introductionmentioning

confidence: 99%

Skeletal disproportion in glucocorticoid-treated boys with Duchenne muscular dystrophy

et al. 2019

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We aimed to compare body segment and bone lengths in glucocorticoid-treated boys with Duchenne muscular dystrophy (DMD) with healthy controls using dual-energy absorptiometry (DXA) images. Total height (Ht), sitting height (SH), leg length (LL) and bone lengths (femur, tibia) in boys with DMD and age-matched control boys were measured using DXA . Thirty boys with DMD (median age 10.0 years (6.1, 16.8)) were compared with 30 controls. SH in DMD was 3.3 cm lower (95% CI − 6.1, − 0.66; p = 0.016). LL in DMD was 7.3 cm lower (95% CI − 11.2, − 3.4; p < 0.0001). SH:LL of boys with DMD was higher by 0.08 (95% CI 0.04, 0.12; p < 0.0001). Femur length in DMD was 2.4 cm lower (95% CI − 4.6, − 0.12; p = 0.04), whereas tibial length in DMD was 4.8 cm lower (95% CI − 6.7, − 2.9; p < 0.0001). SH:LL was not associated with duration of glucocorticoid use (SH:LL β = 0.003, 95% CI − 0.01 to 0.002, p = 0.72). Conclusion : Glucocorticoid-treated boys with DMD exhibit skeletal disproportion with relatively shorter leg length and more marked reduction of distal long bones. As glucocorticoid excess is not associated with such disproportion, our findings raise the possibility of an intrinsic disorder of growth in DMD. What is Known • Severe growth impairment and short stature are commonly observed in boys with Duchenne muscular dystrophy (DMD), especially those treated with long-term glucocorticoids (GC). • In other groups of children with chronic conditions and/or disorders of puberty, skeletal disproportion with lower spinal length has been reported. What is New • Growth impairment in GC-treated boys with DMD was associated with skeletal disproportion in relation to age, with lower limbs and distal long bones affected to a greater degree. Electronic supplementary material The online version of this article (10.1007/s00431-019-03336-5) contains supplementary material, which is available to authorized users.

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“…Although progression of DMD can be slowed with the administration of glucocorticoids (GCs), therapy is often associated with growth retardation and skeletal fragility (Biggar et al, 2006;Joseph et al, 2019). However, it is clear that growth impairment and fractures are also prevalent in steroid-naïve boys with DMD (Rapaport et al, 1991;Larson and Henderson, 2000;Matsumoto et al, 2017), suggesting that there may be an intrinsic abnormality of growth and skeletal development in DMD (Eiholzer et al, 1988). Specifically, an older retrospective study that was carried out before GC therapy became standard of care found that 44% of steroid-naïve DMD boys had sustained a fracture (Larson and Henderson, 2000).…”

Section: Introductionmentioning

confidence: 99%

A comparison of the bone and growth phenotype of mdx, mdx:Cmah−/− and mdx:Utrn +/− murine models with the C57BL/10 wild-type mouse

Wood

Suchacki

Hof

et al. 2020

Disease Models &Amp; Mechanisms

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The muscular dystrophy X-linked (mdx) mouse is commonly used as a mouse model of Duchenne muscular dystrophy (DMD). Its phenotype is, however, mild, and other mouse models have been explored. The mdx:Cmah −/− mouse carries a human-like mutation in the Cmah gene and has a severe muscle phenotype, but its growth and bone development are unknown. In this study, we compared male mdx, mdx:Utrn +/− , mdx:Cmah −/− and wild-type (WT) mice at 3, 5 and 7 weeks of age to determine the suitability of the mdx:Cmah −/− mouse as a model for assessing growth and skeletal development in DMD. The mdx:Cmah −/− mice were lighter than WT mice at 3 weeks, but heavier at 7 weeks, and showed an increased growth rate at 5 weeks. Cortical bone fraction as assessed by micro-computed tomography was greater in both mdx and mdx:Cmah −/− mice versus WT mice at 7 weeks. Tissue mineral density was also higher in mdx: Cmah −/− mice at 3 and 7 weeks. Gene profiling of mdx:Cmah −/− bone identified increased expression of Igf1, Igf1r and Vegfa. Both the mdx and mdx:Cmah −/− mice showed an increased proportion of regulated bone marrow adipose tissue (BMAT) but a reduction in constitutive BMAT. The mdx:Cmah −/− mice show evidence of catch-up growth and more rapid bone development. This pattern does not mimic the typical DMD growth trajectory and therefore the utility of the mdx: Cmah −/− mouse for studying growth and skeletal development in DMD is limited. Further studies of this model may, however, shed light on the phenomenon of catch-up growth. This article has an associated First Person interview with the first author of the paper.

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Patients with Duchenne muscular dystrophy are significantly shorter than those with Becker muscular dystrophy, with the higher incidence of short stature in Dp71 mutated subgroup

Cited by 22 publications

References 33 publications

Dystrophin Dp116: A yet to Be Investigated Product of the Duchenne Muscular Dystrophy Gene

Dystrophin Dp116: A yet to Be Investigated Product of the Duchenne Muscular Dystrophy Gene

Skeletal disproportion in glucocorticoid-treated boys with Duchenne muscular dystrophy

A comparison of the bone and growth phenotype of mdx, mdx:Cmah−/− and mdx:Utrn +/− murine models with the C57BL/10 wild-type mouse

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