Novel AP3B1 compound heterozygous mutations in a Japanese patient with Hermansky?Pudlak syndrome type 2
Novel AP3B1 compound heterozygous mutations in a Japanese patient with Hermansky?Pudlak syndrome type 2
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日本 2 型 Hermansky?Pudlak 综合征患者出现新的 AP3B1 复合杂合突变
DOI：
10.1111/1346-8138.15177
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Kawano Yoshifumi
中科院分区：
文献类型：
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作者：
Nishikawa Takuro;Okamura Ken;Moriyama Mizuki;Watanabe Kenji;Ibusuki Atsuko;Sameshima Seiji;Masamoto Izumi;Yamazaki Ieharu;Tanita Kay;Kanekura Takuro;Kanegane Hirokazu;Suzuki Tamio;Kawano Yoshifumi
Hermansky-Pudlak综合征2型（HPS 2）是一种极为罕见的常染色体隐性遗传病，其特征是部分眼皮肤白化病（OCA），由于储存池缺陷和免疫缺陷导致的出血素质。这种疾病是由衔接蛋白3复合物的破坏引起的，衔接蛋白3复合物参与受损的细胞内囊泡转运。在这里，我们报告了亚洲首例1岁女孩HPS 2的病例。除了OCA和中性粒细胞减少症外，她没有其他特殊症状。我们分析了她的血小板功能，使用透射电子显微镜和血小板聚集试验，细胞毒性脱粒试验的自然杀伤（NK）细胞和出血时间，其结果导致HPS 2的诊断。虽然她的NK细胞细胞毒性脱粒受损，但她没有出现噬血细胞性淋巴组织细胞增多症（HLH）或纤维化肺病的体征。分子遗传学分析显示AP 3B 1中存在新的杂合突变（c.188T>A [p.M63K]和c.2546>A [p.L849X]）。当检查OCA患者时，应进行血液检查以确认中性粒细胞计数、出血时间和血小板凝集。当怀疑HPS 2时，应考虑进行详细的免疫学检查，并应立即和长期关注HLH和肺部病变。
Hermansky–Pudlak syndrome type 2 (HPS2) is an extremely rare autosomal recessive inherited disease characterized by partial oculocutaneous albinism (OCA), bleeding diathesis due to a storage pool deficiency and immunodeficiency. The disorder is caused by disruption of the adapter protein 3 complex, which is involved in impaired intracellular vesicle transport. Here, we report the first case of a 1‐year‐old girl with HPS2 in Asia. She had no specific symptoms other than OCA and neutropenia. We analyzed her platelet function using transmission electron microscopy and a platelet aggregation test, cytotoxic degranulation assay of her natural killer (NK) cells and bleeding time, the results of which led to the diagnosis of HPS2. Although her NK‐cell cytotoxic degranulation was impaired, she had not developed signs of hemophagocytic lymphohistiocytosis (HLH) or fibrosing lung disease. Molecular genetic analyses showed novel heterozygous mutations (c.188T>A [p.M63K] and c.2546>A [p.L849X]) inAP3B1. When examining patients with OCA, blood tests should be performed to confirm neutrophil count, bleeding time and platelet agglutination. When HPS2 is suspected, detailed immunological tests should be considered, and attention should be paid to HLH and pulmonary lesions immediately and over the long term.