Tandem duplication of DMD exon 18 associated with epilepsy, macroglossia, and endocrinologic abnormalities

Muscle Nerve. 2007 Mar;35(3):396-401. doi: 10.1002/mus.20705.

Abstract

We describe a patient with Duchenne muscular dystrophy (DMD) who additionally suffered from intractable seizures, severe mental retardation, and a marked macroglossia. He also had endocrinologic abnormalities consisting of growth hormone deficiency, delayed puberty, and adrenal hypoplasia. We detected a duplication of DMD exon 18 and flanking introns that caused a frame-shift and was not removed by corrective splicing. A coincident mutation in the FKRP gene was excluded by direct sequencing. Complex DNA rearrangements, deletions, and duplications >100 kb were excluded through microarray-comparative genomic hybridization (CGH), although we were not able to exclude a second coincident mutation with certainty. In conclusion, we present a case of DMD that conflicts with current understanding of genotype-phenotype relations and discuss putative pathogenetic mechanisms for this uncommon phenotype.

Publication types

  • Case Reports

MeSH terms

  • Adrenal Insufficiency / genetics
  • Adrenal Insufficiency / metabolism
  • Adrenal Insufficiency / physiopathology
  • Adult
  • DNA Mutational Analysis
  • Dystrophin / genetics*
  • Endocrine System Diseases / complications
  • Endocrine System Diseases / genetics*
  • Endocrine System Diseases / physiopathology
  • Epilepsy / complications
  • Epilepsy / genetics*
  • Epilepsy / physiopathology
  • Exons / genetics
  • Frameshift Mutation / genetics
  • Gene Duplication*
  • Genetic Markers
  • Genotype
  • Growth Hormone / deficiency
  • Humans
  • Intellectual Disability / genetics
  • Intellectual Disability / metabolism
  • Intellectual Disability / physiopathology
  • Macroglossia / complications
  • Macroglossia / genetics*
  • Macroglossia / physiopathology
  • Male
  • Muscular Dystrophy, Duchenne / complications
  • Muscular Dystrophy, Duchenne / genetics*
  • Muscular Dystrophy, Duchenne / physiopathology
  • Pentosyltransferases
  • Phenotype
  • Pituitary Diseases / genetics
  • Pituitary Diseases / metabolism
  • Pituitary Diseases / physiopathology
  • Proteins / genetics
  • Puberty, Delayed / genetics
  • Puberty, Delayed / metabolism
  • Puberty, Delayed / physiopathology
  • Syndrome
  • Tandem Repeat Sequences / genetics

Substances

  • Dystrophin
  • Genetic Markers
  • Proteins
  • Growth Hormone
  • FKRP protein, human
  • Pentosyltransferases