title: The ophthalmic presentation of Hermansky-Pudlak syndrome 6.
abstract: BACKGROUND
  Hermansky-Pudlak syndrome (HPS) may present to the ophthalmologist with signs suggestive of oculocutaneous albinism. Consideration of HPS as a differential diagnosis is important due to its potential systemic complications. HPS6 is a rarely reported subtype.
  
  
  METHODS
  Three patients from two families underwent clinical examination, imaging and targeted systemic investigations. Electrophysiology with visual-evoked potentials (VEPs) was performed in both children of family 1. Whole exome sequencing (WES) was performed on the proband of family 1. Bidirectional Sanger sequencing of the single exon and intron-exon boundaries ofHPS6was performed on all affected patients and segregation confirmed in available relatives.
  
  
  RESULTS
  Two siblings presented in infancy with nystagmus and reduced vision. They were initially diagnosed with isolated foveal hypoplasia with no aberrant chiasmal misrouting on VEPs. WES performed in the proband when 10 years of age identified a novel homozygous missense variant inHPS6and further questioning elicited a history of nose bleeds and mild bruising.Segregation supported causality of this variant in the affected younger sibling. In the third unrelated patient, an initial diagnosis of ocular albinism was made at 3 months with HPS only diagnosed at 26 years. Biallelic, truncating mutations inHPS6were identified by candidate Sanger sequencing and included a novel variant. Abnormal platelet function consistent with HPS was confirmed in all patients.
  
  
  CONCLUSIONS
  The diagnosis of HPS in all patients was delayed due to a mild systemic phenotype. Next-generation sequencing can aid diagnosis of syndromic conditions with important consequences for preventing morbidity.
authors.affiliation: University College London Institute of Ophthalmology, London, UK.|Moorfields Eye Hospital, London, UK.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hull
authors.affiliation: University College London Institute of Ophthalmology, London, UK.|Moorfields Eye Hospital, London, UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Arno
authors.affiliation: University College London Institute of Ophthalmology, London, UK.|Moorfields Eye Hospital, London, UK.
authors.forename: Graham E
authors.initials: GE
authors.lastname: Holder
authors.affiliation: University College London Genetics Institute, London, UK.
authors.forename: Vincent
authors.initials: V
authors.lastname: Plagnol
authors.affiliation: Haematology Department, Royal Free London NHS Foundation Trust, London, UK.
authors.forename: Keith
authors.initials: K
authors.lastname: Gomez
authors.affiliation: Haematology Department, Great Ormond Street Hospital for Children NHS Trust, London, UK.|Haematology Department, University College London Hospitals, London, UK.
authors.forename: Ri
authors.initials: R
authors.lastname: Liesner
authors.affiliation: University College London Institute of Ophthalmology, London, UK.|Moorfields Eye Hospital, London, UK.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster
authors.affiliation: University College London Institute of Ophthalmology, London, UK.|Moorfields Eye Hospital, London, UK.|San Francisco Medical Centre, University of California, San Francisco, California, USA.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D022861:Hermanski-Pudlak Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D010375:Pedigree; D035781:Siblings; D041623:Tomography, Optical Coherence; D055815:Young Adult
chemical_list: C493901:HPS6 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D004247:DNA
keywords: Child health (paediatrics); Diagnostic tests/Investigation; Electrophysiology; Genetics; Retina