Predominance of Dystrophinopathy Genotypes in Mexican Male Patients Presenting as Muscular Dystrophy with A Normal Multiplex Polymerase Chain Reaction DMD Gene Result: A Study Including Targeted Next-Generation Sequencing

Genes (Basel). 2019 Oct 29;10(11):856. doi: 10.3390/genes10110856.


The complete mutational spectrum of dystrophinopathies and limb-girdle muscular dystrophy (LGMD) remains unknown in Mexican population. Seventy-two unrelated Mexican male patients (73% of pediatric age) with clinical suspicion of muscular dystrophy and no evidence of DMD gene deletion on multiplex polymerase chain reaction (mPCR) analysis were analyzed by multiplex ligation-dependent probe amplification (MLPA). Those with a normal result were subjected to Sanger sequencing or to next-generation sequencing for DMD plus 10 selected LGMD-related genes. We achieved a diagnostic genotype in 80.5% (n = 58/72) of patients with predominance of dystrophinopathy-linked genotypes (68%, n = 49/72), followed by autosomal recessive LGMD-related genotypes (types 2A-R1, 2C-R5, 2E-R4, 2D-R3 and 2I-R9; 12.5%, n = 9/72). MLPA showed 4.2% of false-negatives for DMD deletions assessed by mPCR. Among the small DMD variants, 96.5% (n = 28/29) corresponded to null-alleles, most of which (72%) were inherited through a carrier mother. The FKRP p.[Leu276Ile]; [Asn463Asp] genotype is reported for the first time in Mexican patients as being associated with dilated cardiomyopathy. Absence of dysferlinopathies could be related to the small sample size and/or the predominantly pediatric age of patients. The employed strategy seems to be an affordable diagnosis approach for Mexican muscular dystrophy male patients and their families.

Keywords: Duchenne/Becker muscular dystrophies; Mexican population; dilated cardiomyopathy; limb-girdle muscular dystrophies; neuromuscular disorders; next-generation sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Dystrophin / genetics*
  • False Negative Reactions
  • Genetic Testing / methods
  • Genetic Testing / standards*
  • Genotype
  • Humans
  • Male
  • Mexico
  • Multiplex Polymerase Chain Reaction / methods
  • Multiplex Polymerase Chain Reaction / standards
  • Muscular Dystrophy, Duchenne / genetics*
  • Muscular Dystrophy, Duchenne / pathology
  • Mutation*
  • Pentosyltransferases / genetics


  • DMD protein, human
  • Dystrophin
  • FKRP protein, human
  • Pentosyltransferases