Fanconi anemia, Part 2. Methodological strategy for molecular diagnosis in patients with Fanconi anemia

Fanconi anemia (FA) is a rare disease occurring in 1-5/million live births. Patients pres-ent chromosomal instability at the cellular level, which is the basis for their diagnosis, and although clinically they are heterogeneous, there are three general characteristics: alterations in physical development, pancytopenia and high risk of cancer development. To date, 22 genes responsible for FA have been reported, 20 of which are inherited in an autosomal recessive pattern, one autosomal dominant and one X-linked; how-ever, there are genes to be detected, since despite a thorough search, the responsible pathogenic variant cannot be found in all patients. Due to this heterogeneity, the molecular diagnosis is complicated, so a strategy with several methodologies, such as multiple ligand-dependent probe amplification assay (MLPA) and next-generation sequencing, either by directed panel (16 FANC genes) or by whole exome sequencing and high-resolution microarrays, is necessary. With these methodologies, it is possible to detect long deletions or duplications in FANC genes, single nucleotide and copy number alterations, and long regions with homozygosity to find homozygous alleles. In this article, we present a detailed strategy for genotyping Mexican FA patients, with a success rate of 80%.