Gahl W A, Brantly M, Kaiser-Kupfer M I, Iwata F, Hazelwood S, Shotelersuk V, Duffy L F, Kuehl E M, Troendle J, Bernardini I
Heritable Disorders Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892-1830, USA.
N Engl J Med. 1998 Apr 30;338(18):1258-64. doi: 10.1056/NEJM199804303381803.
Hermansky-Pudlak syndrome is characterized by oculocutaneous albinism, a storage-pool deficiency, and lysosomal accumulation of ceroid lipofuscin, which causes pulmonary fibrosis and granulomatous colitis in some cases. All identified affected patients in northwest Puerto Rico are homozygous for a 16-bp duplication in exon 15 of a recently cloned gene, HPS. We compared the clinical and laboratory characteristics of these patients with those of patients without the 16-bp duplication.
Forty-nine patients -- 27 Puerto Ricans and 22 patients from the mainland United States who were not of Puerto Rican descent -- were given a diagnosis on the basis of albinism and the absence of platelet dense bodies. We used the polymerase chain reaction to determine which patients carried the 16-bp duplication.
Twenty-five of the Puerto Rican patients were homozygous for the 16-bp duplication, whereas none of the non-Puerto Rican patients carried this mutation. Like the patients without the duplication, the patients with the 16-bp duplication had a broad variation in pigmentation. Nine of 16 adults with the duplication, but none of the 10 without it, had a diffusing capacity for carbon monoxide that was less than 80 percent of the predicted value. High-resolution computed tomography in 12 patients with the 16-bp duplication revealed minimal fibrosis in 8, moderate fibrosis in 1, severe fibrosis in 1, and no fibrosis in 2. Computed tomography in eight patients without the duplication revealed minimal fibrosis in three and no fibrosis in the rest. Inflammatory bowel disease developed in eight patients (four in each group) between 3 and 25 years of age.
The 16-bp duplication in exon 15 of HPS, which we found only in Puerto Rican patients, is associated with a broad range of pigmentation and an increased risk of restrictive lung disease in adults.
Hermansky-Pudlak综合征的特征为眼皮肤白化病、贮存池缺陷以及类蜡质脂褐素的溶酶体积聚，在某些情况下可导致肺纤维化和肉芽肿性结肠炎。在波多黎各西北部所有已确诊的患病患者中，对于最近克隆的基因HPS外显子15中的一个16碱基对重复序列均为纯合子。我们将这些患者的临床和实验室特征与无该16碱基对重复序列的患者进行了比较。
49例患者——27名波多黎各人以及22名非波多黎各裔的美国大陆患者——根据白化病及血小板致密体缺乏进行诊断。我们使用聚合酶链反应来确定哪些患者携带该16碱基对重复序列。
25名波多黎各患者对于该16碱基对重复序列为纯合子，而无一名非波多黎各患者携带此突变。与无该重复序列的患者一样，有该16碱基对重复序列的患者色素沉着差异很大。16名有该重复序列的成年人中有9名一氧化碳弥散量低于预测值的80%，而10名无该重复序列的成年人中无一例如此。对12名有该16碱基对重复序列的患者进行的高分辨率计算机断层扫描显示，8例有轻微纤维化，1例有中度纤维化，1例有重度纤维化，2例无纤维化。对8名无该重复序列的患者进行的计算机断层扫描显示，3例有轻微纤维化，其余无纤维化。8例患者（每组4例）在3至25岁之间发生了炎症性肠病。
我们仅在波多黎各患者中发现的HPS外显子15中的16碱基对重复序列，与广泛的色素沉着以及成年人限制性肺病风险增加有关。
