X连锁显性遗传性原卟啉症一家系及ALAS2基因突变分析

X-linked dominant protoporphyria：report of a pedigree and detection of ALAS2 gene mutations

目的：报道中国人X连锁显性遗传性原卟啉症一家系，并对其5-氨基酮戊酸合成酶2（ALAS2）基因突变进行研究。方法收集该家系成员资料，进行临床调查。用二代测序方法检测后再行Sanger测序，测定该家系中患病者及部分表型正常者ALAS2致病基因。用皮肤镜观察皮肤卟啉皮损，根据Fotofinder系统和甚高频皮肤超声系统评估皮肤卟啉症的光损伤严重程度，对该家系成员做肝胆B超检查，同时检测血液学改变。结果该家系中所有患者X染色体的1706号到1709号碱基发生AGTG缺失，导致转录时移码突变，最终导致翻译得到的ALAS2酶C端19、20个残基替换或缺失，ALAS2酶活性升高。XLDPP患者皮肤光损伤显著，肝胆可出现卟啉损伤，随年龄增加而加重，可出现贫血和铁过载。结论 X染色体1706-1709碱基AGTG缺失突变可能是该ALDPP家系患者的发病原因。

Objective To report a pedigree with X-linked dominant protoporphyria（XLDPP）, and to detect 5-aminolevulinic acid synthetase 2（ALAS2）gene mutations in this pedigree. Methods A clinical investigation was performed in a pedigree with XLDPP, and relevant data were collected from family members. A next-generation sequencing method was applied to screen possible mutation sites, and Sanger sequencing was performed to determine pathogenic gene mutations. Dermoscopy was conducted to observe skin lesions in the patients with XLDPP, and the Fotofinder system and very high frequency （VHF） ultrasound system were utilized to assess the severity of photodamage. Liver and gallbladder ultrasonography as well as blood examination were performed for all the family members. Results A deletion mutation, c.1706-1709ΔAGTG, was detected in the ALAS2 gene on the X chromosomes of all the patients in this family, which led to replacement or loss of 19-20 C-terminal residues through transcriptional frameshifting, and eventually caused an increase in ALAS2 activity. In the patients with XLDPP, skin photodamage was relatively severe;protoporphyrin-induced hepatobiliary damage was observed and aggravated with age;anemia and iron deficiency occurred sometimes. Conclusion The deletion mutation c.1706-1709ΔAGTG of the ALAS2 gene may be the underlying cause of XLDPP in this pedigree.