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

Research output: Contribution to journalArticle

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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
JournalEuropean Journal of Medical Genetics
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Hermanski-Pudlak Syndrome
Epilepsy
Mutation
Piebaldism
Blood Platelets
Oculocutaneous Albinism
Albinism
Exome
Genetic Databases
Lysosomes
Hair
Seizures
Leukocytes
Skin
Proteins

Keywords

  • AP3D1
  • Hermansky-Pudlak syndrome
  • Immunodeficiency
  • Seizures

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Biallelic mutations in AP3D1 cause Hermansky-Pudlak syndrome type 10 associated with immunodeficiency and seizure disorder. / Mohammed, Mohammed; Al-Hashmi, Nadia; Al-Rashdi, Samiya; Al-Sukaiti, Nashat; Al-Adawi, Kawther; AL-Riyami, Marwa; Al-Maawali, Almundher.

In: European Journal of Medical Genetics, 01.01.2018.

Research output: Contribution to journalArticle

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