Mohammed Mohammed, Al-Hashmi Nadia, Al-Rashdi Samiya, Al-Sukaiti Nashat, Al-Adawi Kawther, Al-Riyami Marwa, Al-Maawali Almundher
Department of Pediatrics, Royal Hospital, Ministry of Health, Muscat, Oman.
Department of Genetics, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
Eur J Med Genet. 2019 Nov;62(11):103583. doi: 10.1016/j.ejmg.2018.11.017. Epub 2018 Nov 22.
Several types of Hermansky-Pudlak syndromes (HPS) represent a group of immunodeficiency syndromes that feature both leukocyte defects with partial albinism of hair, skin, and eyes. These conditions share defects in genes that encode proteins involved in the biogenesis, function, and trafficking of secretory lysosomes. Mutations in AP3D1 which encode the main subunit AP-3(δ) were recently reported on one individual and led to Hermansky-Pudlak Syndrome type 10 (HPS10; OMIM 617050). HPS10 is a severe condition that manifests with symptoms of oculocutaneous albinism, neurodevelopmental delays, platelet dysfunction, and immunodeficiency. Herein we report on three affected individuals who presented with severe seizures, developmental delay, albinism, and immunodeficiency. Whole exome sequencing identified homozygosity for a deleterious sequence variant of high impact in AP3D1, c.1978delG, predicting p.Ala660Argfs*54 (NM_001261826.3). We further demonstrated an abnormal storage pathway in the platelets. The current study represents a second confirmation report and implicates AP3D1 mutations as a cause of Hermansky-Pudlak Syndrome type 10.
几种类型的赫尔曼斯基-普德拉克综合征（HPS）代表了一组免疫缺陷综合征，其特征是白细胞缺陷以及头发、皮肤和眼睛部分白化。这些病症在编码参与分泌性溶酶体生物发生、功能和运输的蛋白质的基因中存在缺陷。最近报道了编码主要亚基AP-3（δ）的AP3D1中的突变，该突变导致了10型赫尔曼斯基-普德拉克综合征（HPS10；OMIM 617050）。HPS10是一种严重病症，表现为眼皮肤白化病、神经发育迟缓、血小板功能障碍和免疫缺陷症状。在此，我们报告了三名受影响个体，他们出现了严重癫痫发作、发育迟缓、白化病和免疫缺陷。全外显子组测序确定了AP3D1中一个具有高影响的有害序列变异c.1978delG的纯合性，预测为p.Ala660Argfs*54（NM_001261826.3）。我们进一步证明了血小板中存在异常的储存途径。本研究是第二项确认报告，表明AP3D1突变是10型赫尔曼斯基-普德拉克综合征的病因。
