Deptartment of Biochemistry, Medical Sciences Campus, School of Medicine, University of Puerto Rico, San Juan, Puerto Rico.
Comprehensive Cancer Center, University of Puerto Rico, San Juan, Puerto Rico.
Mol Genet Genomic Med. 2024 Jul;12(7):e2493. doi: 10.1002/mgg3.2493.
Albinism is a heterogeneous condition in which patients present complete absence, reduction, or normal pigmentation in skin, hair and eyes in addition to ocular defects. One of the heterogeneous forms of albinism is observed in Hermansky-Pudlak syndrome (HPS) patients. HPS is characterized by albinism and hemorrhagic diathesis due to the absence of dense bodies in platelets.
In this report, we describe a case of a pair of Puerto Rican siblings with albinism that were clinically diagnosed with HPS during childhood. Since they did not harbor the founder changes in the HPS1 and HPS3 genes common in Puerto Ricans, as adults they wanted to know the type of albinism they had. We performed exome sequencing, validation by PCR, and cloning of PCR products followed by Sanger sequencing in the family members.
We discovered no mutations that could explain an HPS diagnosis. Instead, we found the siblings were compound heterozygotes for 4 variants in the Tyrosinase gene: c.-301C>T, c.140G>A (rs61753180; p.G47D), c.575C>A (rs1042602; p.S192Y), and c.1205G>A (rs1126809; p.R402Q). Our results show that the correct diagnosis for the siblings is OCA1B.
Our study shows the importance of molecular testing when diagnosing a rare genetic disorder, especially in populations were the disease prevalence is higher.
白化病是一种异质性疾病，患者除了眼部缺陷外，皮肤、头发和眼睛完全缺乏、减少或正常色素沉着。白化病的一种异质性形式见于 Hermansky-Pudlak 综合征（HPS）患者中。HPS 的特征是由于血小板中致密体缺失而导致白化病和出血倾向。
在本报告中，我们描述了一对患有白化病的波多黎各兄弟姐妹的病例，他们在儿童时期被临床诊断为 HPS。由于他们没有携带在波多黎各人中常见的 HPS1 和 HPS3 基因的创始人变化，成年后他们想知道自己患有的是哪种白化病。我们进行了外显子组测序，对 PCR 产物进行了验证和克隆，然后对家庭成员进行了 Sanger 测序。
我们没有发现可以解释 HPS 诊断的突变。相反，我们发现兄弟姐妹是酪氨酸酶基因的 4 种变体的复合杂合子：c.-301C>T、c.140G>A（rs61753180；p.G47D）、c.575C>A（rs1042602；p.S192Y）和 c.1205G>A（rs1126809；p.R402Q）。我们的结果表明，兄弟姐妹的正确诊断是 OCA1B。
我们的研究表明，在诊断罕见遗传疾病时，特别是在疾病流行率较高的人群中，分子检测非常重要。
