title: Hermansky-Pudlak syndrome type 1 in patients of Indian descent.
abstract: Hermansky-Pudlak syndrome (HPS) develops from defects in the biogenesis and/or function of lysosome-related organelles essential to membrane and protein trafficking. Of the eight known human subtypes, only HPS-1 and HPS-4 develop pulmonary fibrosis in addition to the general clinical manifestations of oculocutaneous albinism and bleeding diathesis. We identified HPS-1 in three unrelated patients from different regions of India, who presented with iris transillumination, pale fundi, hypopigmentation, nystagmus, decreased visual acuity, and a bleeding diathesis. Two of these patients carried the homozygous mutation c.398+5G>A (IVS5+5G>A) in HPS1, resulting in skipping of exon 5 in HPS1 mRNA. The third patient carried a novel homozygous c.988-1G>T mutation that resulted in in-frame skipping of HPS1 exon 12 and removes 56 amino acids from the HPS1 protein. Given the discovery of HPS-1 in an ethnic group where oculocutaneous albinism (OCA) is highly prevalent, it is possible that HPS in India is under-diagnosed. We recommend that unconfirmed OCA patients in this ethic group be considered for mutational screening of known HPS genes, in particular c.398+5G>A and c.980-1G>T, to ensure that patients can be monitored and treated for clinical complications unique to HPS.
authors.affiliation: Section on Human Biochemical Genetics, Medical Genetics Branch, NHGRI, NIH, 10 Center Drive, Bldg. 10, Rm 10C107, MSC1851, Bethesda, MD 20892-1851, USA. vincentl@mail.nih.gov
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Vincent
authors.forename: David
authors.initials: D
authors.lastname: Adams
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hess
authors.forename: Shira G
authors.initials: SG
authors.lastname: Ziegler
authors.forename: Ekaterini
authors.initials: E
authors.lastname: Tsilou
authors.forename: Gretchen
authors.initials: G
authors.lastname: Golas
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: O'Brien
authors.forename: James G
authors.initials: JG
authors.lastname: White
authors.forename: Marjan
authors.initials: M
authors.lastname: Huizing
authors.forename: William A
authors.initials: WA
authors.lastname: Gahl
mesh_terms: D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D001792:Blood Platelets / Q000648:ultrastructure; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics*; D006801:Humans; D007194:India; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data
chemical_list: C102160:HPS1 protein, human; D008565:Membrane Proteins