A woman with blistering skin and abnormal CBC findings with a novel mutation resulting in aberrant splice of PPOX transcript
Biochemical/Metabolic and Therapeutics
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Primary Categories:
- Clinical Genetics
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Secondary Categories:
- Clinical Genetics
Introduction
Porphyria Variegata (OMIM#176200) is a rare metabolic disorder characterized by deficient function of protoporphyrinogen oxidase (PPOX gene product). The inheritance pattern is autosomal dominant with variable expressivity. NGS testing identified a variant within the PPOX gene (c.807+2T>C, splice donor). Currently only 1 known case is identified in ClinVar database with assignment of variant of likely pathogenic. Here, we conducted sequence analysis of the transcripts and determine the mutation resulting in skipping exon 9 resulting in obliterate of gene function by prediction.
Case Presentation
The proband is an East Asian female age 43, with 15 years of unexplained blisters and hyperpigmentation of her hands and sun-exposed facial area. Acute attacks of abdominal pain and vomiting of unknown etiology are also present in irregular frequency.
Diagnostic Workup
CBC showed abnormal finding most promintely with widen RDW and microcytic anemia. NGS based genetic test containing 10 genes (ALAD, ALAS2, CLPX, CPOX, FECH, GATA1, HMBS, PPOX, UROD, UROS) involved in the porphyria gene family are ordered. The NGS identified a variant within the PPOX gene (c.807+2T>C (splice donor)).
Treatment and Management
None
Outcome and Follow-Up
None
Discussion
The result suggest the potential of PPOX c.807+2T>C mutation playing a role in the deficiency of PPOX gene function. Together, this bolster the possibility of the mutation’s involvement in proband’s clinical manifestation. Expanded study are currently underway.
Conclusion
Since variegata porphyria is the consequence of PPOX gene in the porphyria pathway. A biochemical testing using mass-spec analysis of the upstream porphyria intermediate protein is underway to investigate the possibility of early sign of acute attack.
Porphyria Variegata (OMIM#176200) is a rare metabolic disorder characterized by deficient function of protoporphyrinogen oxidase (PPOX gene product). The inheritance pattern is autosomal dominant with variable expressivity. NGS testing identified a variant within the PPOX gene (c.807+2T>C, splice donor). Currently only 1 known case is identified in ClinVar database with assignment of variant of likely pathogenic. Here, we conducted sequence analysis of the transcripts and determine the mutation resulting in skipping exon 9 resulting in obliterate of gene function by prediction.
Case Presentation
The proband is an East Asian female age 43, with 15 years of unexplained blisters and hyperpigmentation of her hands and sun-exposed facial area. Acute attacks of abdominal pain and vomiting of unknown etiology are also present in irregular frequency.
Diagnostic Workup
CBC showed abnormal finding most promintely with widen RDW and microcytic anemia. NGS based genetic test containing 10 genes (ALAD, ALAS2, CLPX, CPOX, FECH, GATA1, HMBS, PPOX, UROD, UROS) involved in the porphyria gene family are ordered. The NGS identified a variant within the PPOX gene (c.807+2T>C (splice donor)).
Treatment and Management
None
Outcome and Follow-Up
None
Discussion
The result suggest the potential of PPOX c.807+2T>C mutation playing a role in the deficiency of PPOX gene function. Together, this bolster the possibility of the mutation’s involvement in proband’s clinical manifestation. Expanded study are currently underway.
Conclusion
Since variegata porphyria is the consequence of PPOX gene in the porphyria pathway. A biochemical testing using mass-spec analysis of the upstream porphyria intermediate protein is underway to investigate the possibility of early sign of acute attack.