ABSTRACT
BACKGROUND: Autosomal recessive congenital ichthyoses (ARCI) are inherited disorders produced by mutations in essential genes for the skin function. A low prevalence of this disease has been resported worldwide; however, in a recent study, we identified a large cluster of ARCI families who resided in the High Mountains Region from the Veracruz State, Mexico. Thus, we aimed to identify the causative mutation of ARCI and describe the high prevalence of this disease in this region. METHODS: We selected seven familiar trios and performed whole-exome sequencing to identify the mutation associated with ARCI. To validate the identified mutation, we performed Sanger sequencing in 62 patients, 30 unaffected relatives, and 100 healthy volunteers. Finally, we performed molecular modeling to investigate the possible functional consequences produced by the mutation. RESULTS: We identified a novel homozygous mutation (c.1054C>G [p.Pro352Ala]) in the exon 7 of the TGM1 gene in all the patients. We calculated a prevalence rate of ARCI of 74:100,000 (1:1,348) in the studied communities. Molecular modeling revealed that the mutation leads to a nonconservative amino acid substitution, which is very probably damaging to the protein structure/function. CONCLUSIONS: We report a novel mutation in the TGM1 gene in 62 Mexican patients. The unusually high frequency of this mutation suggests a founder effect; however, further haplotype analysis is necessary to corroborate this hypothesis. In this respect, to our knowledge, the prevalence of ARCI found in the studied communities is the highest observed worldwide.
