Dystrophinopathy Phenotypes and Modifying Factors in DMD Exon 45-55 Deletion.

OBJECTIVE: Duchenne muscular dystrophy (DMD) exon 45-55 deletion (del45-55) has been postulated as a model that could treat up to 60% of DMD patients, but the associated clinical variability and complications require clarification. We aimed to understand the phenotypes and potential modifying factors of this dystrophinopathy subset. METHODS: This cross-sectional, multicenter cohort study applied clinical and functional evaluation. Next generation sequencing was employed to identify intronic breakpoints and their impact on the Dp140 promotor, intronic long noncoding RNA, and regulatory splicing sequences. DMD modifiers (SPP1, LTBP4, ACTN3) and concomitant mutations were also assessed. Haplotypes were built using DMD single nucleotide polymorphisms. Dystrophin expression was evaluated via immunostaining, Western blotting, reverse transcription polymerase chain reaction (PCR), and droplet digital PCR in 9 muscle biopsies. RESULTS: The series comprised 57 subjects (23 index) expressing Becker phenotype (28%), isolated cardiopathy (19%), and asymptomatic features (53%). Cognitive impairment occurred in 90% of children. Patients were classified according to 10 distinct index-case breakpoints; 4 of them were recurrent due to founder events. A specific breakpoint (D5) was associated with severity, but no significant effect was appreciated due to the changes in intronic sequences. All biopsies showed dystrophin expression of >67% and traces of alternative del45-57 transcript that were not deemed pathogenically relevant. Only the LTBP4 haplotype appeared associated the presence of cardiopathy among the explored extragenic factors. INTERPRETATION: We confirmed that del45-55 segregates a high proportion of benign phenotypes, severe cases, and isolated cardiac and cognitive presentations. Although some influence of the intronic breakpoint position and the LTBP4 modifier may exist, the pathomechanisms responsible for the phenotypic variability remain largely unresolved. ANN NEUROL 2022;92:793-806.

Traumatic dental injuries among schoolchildren in Valencia, Spain.

AIM: The aim of the present study was to identify some factors related to the occurrence of dental trauma in mixed and permanent dentition. DESIGN OF THE STUDY: Over a period of two months 1325, 6 to 18 year olds from three primary schools in Valencia were examined. Data was collected through clinical examinations and interviews and their Dental trauma was classified according to IADT's criteria. RESULTS: The prevalence of dental injuries was 6%; boys aged between 12-18 years old experienced more injuries than girls. There was a statistical difference between the types of fractures. Non complicated coronal fractures were the most frequent (9.18%). Games were the main cause of trauma (40%) in both sexes. In 14.3% of patients a dental colour change was observed. Angle's class I was the most frequent in traumatized injured children (41.2%). CONCLUSIONS: The present study revealed a relatively low prevalence of dental trauma, but this figure still represents a large number of children. Therefore, educational programs are to be initiated for the community regarding causes , prevention and treatments of traumatic dental injuries.

Comparison of the clinical effects of white brand toothbrushes versus Vitis Suave®.

BACKGROUND: There has been an increase in the use of white label manual toothbrushes and a greater increase in inquiries for discomfort of the gingiva and mucosa. MATERIAL AND METHODS: A randomized, double-blind, cross-over clinical trial was made of four white brand toothbrushes versus a control brush (Vitis Suave®), with the recording of plaque index, bleeding upon probing, and gingival abrasions following utilization of the different brushes. RESULTS: All the brushes except Deliplus® were equally effective in terms of plaque removal (p<0.05). Vitis Suave® and Veckia® were the brushes associated to the greatest increase in minor abrasions (p<0.01), while Veckia®, Carrefour® and Deluxe® significantly increased the number of medium intensity abrasions (p<0.05). These brushes also increased the number of large abrasions, though statistical significance was not reached in this case. CONCLUSIONS: The white brand brushes proved effective in controlling bacterial plaque, but were associated to more intense soft tissue abrasion. KEY WORDS: Gingival abrasions, manual tooth brushing, white brand, clinical effects.