Biallelic mutations in AP3D1 cause Hermansky-Pudlak syndrome type 10 associated with immunodeficiency and seizure disorder

Mohammed Mohammed, Nadia Al-Hashmi, Samiya Al-Rashdi, Nashat Al-Sukaiti, Kawther Al-Adawi, Marwa Al-Riyami, Almundher Al-Maawali*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

Several types of Hermansky-Pudlak syndromes (HPS) represent a group of immunodeficiency syndromes that feature both leukocyte defects with partial albinism of hair, skin, and eyes. These conditions share defects in genes that encode proteins involved in the biogenesis, function, and trafficking of secretory lysosomes. Mutations in AP3D1 which encode the main subunit AP-3(δ) were recently reported on one individual and led to Hermansky-Pudlak Syndrome type 10 (HPS10; OMIM 617050). HPS10 is a severe condition that manifests with symptoms of oculocutaneous albinism, neurodevelopmental delays, platelet dysfunction, and immunodeficiency. Herein we report on three affected individuals who presented with severe seizures, developmental delay, albinism, and immunodeficiency. Whole exome sequencing identified homozygosity for a deleterious sequence variant of high impact in AP3D1, c.1978delG, predicting p.Ala660Argfs*54 (NM_001261826.3). We further demonstrated an abnormal storage pathway in the platelets. The current study represents a second confirmation report and implicates AP3D1 mutations as a cause of Hermansky-Pudlak Syndrome type 10.

Original languageEnglish
Article number103583
JournalEuropean Journal of Medical Genetics
Volume62
Issue number11
DOIs
Publication statusPublished - Nov 2019

Keywords

  • AP3D1
  • Hermansky-Pudlak syndrome
  • Immunodeficiency
  • Seizures

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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