NGS-based 100-gene panel of hypopigmentation identifies mutations in Chinese Hermansky-Pudlak syndrome patients.
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.
Department of Dermatology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Aihua
A
Wei
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics & Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Yefeng
Y
Yuan
Department of Ophthalmology, Beijing Childrens Hospital, Capital Medical University, Beijing, China.
Dayong
D
Bai
Center for Medical Genetics, Beijing Childrens Hospital, Capital Medical University, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Beijing, China.
Jing
J
Ma
Center for Medical Genetics, Beijing Childrens Hospital, Capital Medical University, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Beijing, China.
Zhenhua
Z
Hao
Department of Dermatology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Yingzi
Y
Zhang
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics & Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Jiaying
J
Yu
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics & Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Zhiyong
Z
Zhou
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics & Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Lin
L
Yang
Department of Dermatology, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
Xiumin
X
Yang
Department of Ophthalmology, Beijing Childrens Hospital, Capital Medical University, Beijing, China.
Li
L
Li
Center for Medical Genetics, Beijing Childrens Hospital, Capital Medical University, Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Beijing, China.|Center of Alzheimer's Disease, Beijing Institute for Brain Disorders, Beijing, China.
Wei
W
Li
D033963:Adaptor Protein Complex 3 / Q000235:genetics; D033966:Adaptor Protein Complex beta Subunits / Q000235:genetics; D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D022861:Hermanski-Pudlak Syndrome / Q000175:diagnosis* / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D017496:Hypopigmentation / Q000235:genetics*; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D010375:Pedigree
C439973:AP3B1 protein, human; D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits; D015415:Biomarkers; D002352:Carrier Proteins; C102160:HPS1 protein, human; C432680:HPS3 protein, human; C493900:HPS5 protein, human; C493901:HPS6 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins
Hermansky-Pudlak syndrome; albinism; lysosome-related organelles; next-generation sequencing; previouslyunreported alleles