Neuropediatrics 2017; 48(06): 442-450
DOI: 10.1055/s-0037-1607054
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Molecular Analysis Confirms that FKRP-Related Disorders are Underdiagnosed in Mexican Patients with Neuromuscular Diseases

María José Navarro-Cobos1, *, Ariadna González-del Angel2, *, Bernardette Estandia-Ortega2, Adriana Ruiz-Herrera3, Arturo Becerra4, Guadalupe Vargas-Ramírez5, Cesárea Bermúdez-López2, Miguel Angel Alcántara-Ortigoza2
  • 1Maestría en Ciencias Biológicas (Biomedicina)-Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México. Ciudad de México, México
  • 2Laboratorio de Biología Molecular, Departamento de Genética Humana, Instituto Nacional de Pediatría, Ciudad de México, México
  • 3Servicio de Genética Médica, Hospital de Especialidades Pediátrico de León, Guanajuato, México
  • 4Facultad de Ciencias, Universidad Nacional Autónoma de México, Ciudad de México, México
  • 5Servicio de Neurología Pediátrica, Hospital de Especialidades Pediátrico de León, Guanajuato, México
Further Information

Publication History

23 June 2017

21 August 2017

Publication Date:
24 October 2017 (eFirst)


The FKRP-related disorders include the limb-girdle muscular dystrophy type 2I (LGMD2I, MIM#607155) which has a clinical overlap with dystrophinopathies. Except for Brazil, LGMD2I has not been described in other Latin-American countries, despite that 1/64 Mexican-ancestry individuals carry the commonest European p.(Leu276Ile) pathogenic FKRP variant (rs28937900, 1000 Genomes Project Phase 3), suggesting an underdiagnosis. Sequencing of exon 4 of FKRP in 60 unrelated Mexican patients with presumptive diagnoses of dystrophinopathy without DMD gene deletions, or with a neuromuscular disorder of unknown etiology, revealed two patients (2/60, 3.3%): one of them with an unreported pathogenic genotype, p.[Leu276Ile];[Asn463Asp] and a Duchenne-like phenotype; and the other that stands as the third reported case bearing the severe genotype, p.[Asn463Asp];[Asn463Asp] leading to a congenital presentation (MIM#606612). We identified two patients heterozygous for the p.(Arg143Ser) and the novel p.(Arg48Pro) variants, respectively, which were absent in 200 control alleles. Protein modeling suggests that p.(Arg143Ser) is a tolerated change, while p.(Arg48Pro) induces a structural modification, although further molecular confirmation of dystrophinopathy was obtained in the p.(Arg48Pro) patient. Our results justify the inclusion of FKRP-related disorders in the differential diagnosis of Mexican neuromuscular patients. The commonly reported heterozygous FKRP genotypes deserve attention to avoid LGMD2I molecular misdiagnosis.


This work was performed at the Instituto Nacional de Pediatría, Ciudad de México, México. The World Wide Web resources that were consulted are provided as [Supplementary Material], available online-only.

* First authors who contributed equally to this work.

Supplementary Material