LAUSR

&NA; 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.