Background She is born hypotonic and maintains muscle weakness and digestive problems with vomiting, recurrent anemia, photosensitivity, fatigue, drowsiness and respiratory failure associated with outbreaks suffering numerous hospital admissions; with age appear muscular tonic problems and osteopenia (resistant to treatment). She was clinically and biochemically diagnosed of Porphyria without having found the causal gene after various targeted studies.

Material and Methods Starting from a blood sample in EDTA, the DNA was extracted by automatic thecnique based on magnetic beads. The human whole exome was performed by massive sequencing with ‘Twist Human Core Exome’ that amplifies 21,528 genes; using Illumuna’s NextSeq 2000^TM Sequencing System Platform.

Results Three heterozygous variants were found in relation to their pluripathological involvement: a novel PPOX gene variant (NM_001122764) c.604del; p.Leu202Cysfs*32, (Not described in ClinVar nor in dbSNP, with ACMG criteria PVS1,PM2 it is probably pathogenic). Another in gene LGR4 (NM_018490) c.1087G>T; p.Gly363Cys, described as pathogenic in ClinVar rs117543292. And in gene MYO1H (NM_001101421) c.242+1G>A, rs559770546 (Not described in ClinVar, with ACMG criteria PVS1, PM2 it is probably pathogenic).

Conclusions The PPOX gene explains Variegata Porphyria by dominant inheritance; The LGR4 gene explains the decreased in bone mineral density with dominant inheritance and the MYO1H gene would explain its respiratory failure, although recessive inheritance. It is not ruled out that in situations of metabolic stress the penetrance may be partial even in heterozygosity. Concluding that each patient is unique and their different symptoms become clearer as more of their genome is studied.