NGS‐based 100‐gene panel of hypopigmentation identifies mutations in Chinese Hermansky–Pudlak syndrome patients

Abstract

Hermansky-Pudlak syndrome (HPS) is a rare recessive disorder characterized by hypopigmentation, bleeding diathesis, and other symptoms due to multiple defects in lysosome-related organelles. Ten HPS subtypes have been identified with mutations in HPS1 to HPS10. Only four patients with HPS-1 have been reported in Chinese population. Using next-generation sequencing (NGS), we have screened 100 hypopigmentation genes and identified four HPS-1, two HPS-3, one HPS-5, and three HPS-6 in Chinese HPS patients with typical ocular or oculocutaneous albinism and the absence of platelet dense granules together with other variable phenotypes. All these patients except one homozygote were compound heterozygotes. Among these mutations, 14 were previously unreported alleles (four in HPS1, three in HPS3, two in HPS5, five in HPS6). Our results demonstrate the feasibility and utility of NGS-based panel diagnostics for HPS. Genotyping of HPS subtypes is a prerequisite for intervention of subtype-specific symptoms.

Characterization of melanosomes and melanin in Japanese patients with Hermansky–Pudlak syndrome types 1, 4, 6, and 9

“…In the mouse study, all skin samples were harvested from 4‐week‐old mice (Nguyen et al., ), while we examined hair samples from both adolescents and adults. Generally, the hair and skin of individuals affected with HPS1 darkens as the patient ages, and a similar tendency was also reported in HPS patients with BLOC‐2 mutations (Wei, ; Wei et al., ). One of the reasons why our HPS9 patient (52 yr) showed less severe hair conditions than HPS1‐1 (14 yr) and HPS1‐2 (12 yr) might be the age at which the samples were taken.…”

“…She has compound heterozygous truncating mutations [c. 60_64dupGCGGC (p.L22RfsX33) and c.2038C>T (p.Q680X)] in HPS6 (GenBank Accession number: NM_024747.5). The c.60_64dupGCGGC mutation has already been reported as c.64_65insGCGGC (Wei et al., ), whereby the former description conforms recommendations by the Human Genome Variation Society (HGVS) (http://www.hgvs.org/). The c.2038C>T (p.Q680X) nonsense mutation has also been previously reported in a Japanese patient (Miyamichi et al., ).…”

Hermansky–Pudlak syndrome: Mutation update

“…HPS is a rare autosomal recessive disorder characterized by genetic and phenotypic heterogeneity. With the recent rapid evolution of affordable next‐generation sequencing methods, there is increased recognition of HPS subjects and new HPS genetic subtypes (Arcot Sadagopan et al, 2017; Wei et al, 2016; Yousaf et al, 2016). This is also evidenced by the increased diagnosis of subjects with nonclassic HPS phenotypes (i.e., HPS‐2, HPS‐7, HPS‐8, HPS‐9, and HPS‐10; Ammann et al, 2016; Bryan et al, 2017; Cetica et al, 2015; Iwata et al, 2017; Okamura et al, 2018), as well as diagnosis of “unexpected” HPS in cohorts with albinism (S. Ito et al, 2005; Khan et al, 2016), immunodeficiency (Badolato et al, 2012), ocular disease (Hull et al, 2016; Miyamichi et al, 2016), or platelet disorders (Jones et al, 2012).…”

“…HPS‐3 is common in central Puerto Rico, where about one in 4,000 individuals are affected (Anikster et al, 2001; Santiago Borrero et al, 2006). Individuals with HPS have been described in many other regions, including China, India, South America, and Western Europe (Arcot Sadagopan et al, 2017; Carmona‐Rivera, Golas et al, 2011; Hermos, Huizing, Kaiser‐Kupfer, & Gahl, 2002; Wei et al, 2016).…”

Identification of two Chinese oculocutaneous albinism type 6 patients and mutation updates of the SLC24A5 gene

“…All OCA patients were from different Chinese provinces and next‐generation sequencing was performed on all …”