X-linked dominant protoporphyria in a Chinese pedigree reveals a four-based deletion of ALAS2

BACKGROUND: X-linked dominant protoporphyria (XLDPP) is a rare, hereditary disorder that leads to hepatobiliary and hematologic abnormalities including increased erythrocyte protoporphyrin, cutaneous photosensitivity, and decreased iron stores that is caused by a pathogenic mutation of ALAS2 gene. METHODS: This study aimed to confirm the existence of XLDPP in a Chinese pedigree. We observed and described the dermatoscopic findings of this disorder under dermoscopy, and assessed photo damage in XLDPP patients using the Fotofinder system and very high frequency (VHF) skin ultrasonic system. We performed next generation sequencing and Sanger sequencing to detect and confirm genetic variants in DNA samples from the XLDPP family. Moreover, we monitored the hepatobiliary function as well as hematologic changes in related family members. RESULTS: As compared to unaffected control subjects, patients exhibited evidence of severe cutaneous photodamage, causing photoaging, an increase in the size of the gallbladder, increased levels of protoporphyrin in red blood cells, an increase in blood levels of uroporphyrin and hematoporphyrin, and iron deficiency. CONCLUSIONS: XLDPP was validated by the identification of a four-base-pair deletion (c.1706_1709delAGTG, p.E569fs) in ALAS2 (NM_000032.4) in the proband which segregated with the disease in an X-linked dominant pattern, with hemizygous males being more severely affected than heterozygous females. We also found a missense variant in GATA Binding Protein 1 (GATA1).