Loss of Dp140 regulatory sequences is associated with cognitive impairment in dystrophinopathies

Alessandra Bardoni, Giorgio Felisari, Manuela Sironi, Giacomo Comi, Monica Lai, Micaela Robotti, Nereo Bresolin

Research output: Contribution to journalArticlepeer-review

Abstract

Mental retardation is a clinical feature present in both Duchenne and Becker muscular dystrophy patients and its pathogenesis is still unknown. Dp140 is a dystrophin isoform with predominant expression during foetal brain development. Its promoter and first exon lie in the large intron between exon 44 and 45, a region that is commonly deleted in dystrophinopathic patients. We performed neuropsychological evaluation and genetic analysis of the Dp140 transcription unit on 12 Duchenne muscular dystrophy and 28 Becker muscular dystrophy patients carrying deletions in this critical region. Comparison of neuropsychological and molecular data showed that there is a statistically significant relationship between the loss of Dp140 transcription unit and mental retardation in Becker muscular dystrophy patients (P=0.008). Such a correlation is not evident in Duchenne muscular dystrophy patients but only shows a trend towards significance (P=0.063). It is worth noting that both Duchenne muscular dystrophy and Becker muscular dystrophy patients with normal intelligence do not show deletions in the Dp140 regulatory regions. In the light of these findings, we suggest that impairment of cognitive abilities in Duchenne muscular dystrophy and Becker muscular dystrophy patients might be related to a dysfunction of Dp140 brain isoform. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)194-199
Number of pages6
JournalNeuromuscular Disorders
Volume10
Issue number3
DOIs
Publication statusPublished - Mar 1 2000

Keywords

  • Dp140 isoform
  • Duchenne and Becker muscular dystrophies
  • Mental retardation

ASJC Scopus subject areas

  • Clinical Neurology
  • Pediatrics, Perinatology, and Child Health
  • Developmental Neuroscience
  • Neurology

Fingerprint Dive into the research topics of 'Loss of Dp140 regulatory sequences is associated with cognitive impairment in dystrophinopathies'. Together they form a unique fingerprint.

Cite this