分子遺伝医学

A Novel Non-Sense Mutation in a Senegalese Patient with Hermansky-Pudlak Type 1 Syndrome

Abstract

Ndiaye R, Dia Y, Lasseaux E, Mbaye S, Plaisant C, Diop JPD, Ba SA, Mbengue B, Ly F, Arveiler B and Dieye A

Hermansky-Pudlak syndrome (HPS) is a rare inherited multisystem disorder characterized by oculocutaneous albinism and diathesis, and in some patients with pulmonary fibrosis. It is caused by defective biogenesis and trafficking of lysosome-related organelles. Genetically HPS is heterogeneous, and ten loci have been identified as causative genes. The majority of these genes encode subunits of multi-protein complexes named biogenesis of lysosomes-related organelles complex. Mutations within HPS1 and HPS4 genes lead to pulmonary fibrosis in HPS type1 and type 4 patients respectively and are the leading cause of mortality. A 14 years Senegalese boy who was initially diagnosed with oculocutaneous albinism was recruited with his father after informed consent for genetic analysis. In his clinical history, there was no bleeding tendency or clinical episodes of hemorrhagic diathesis. One of his sisters had albinism and died from lung complications at the age of 15 years. The patient was referred to the pneumology department of Fann Hospital in Dakar for further explorations. The high-resolution computed tomography (HRCT) scans of the lungs revealed no evidence of diffuse interstitial lung disease, pleuropericardial effusion, bronchiectasis, pulmonary hypertension, intra pulmonary/mediastinal mass or lymphadenopathy. Mutation screening by Albinism NGS panel identified a homozygous mutation located in exon 6 of the HPS1 gene, c.421C˃T (p.Gln141*), in the Proband while his father showed heterozygosity for this mutation. The parents of the proband are not consanguineous and this may suggest a common allele of HPS1 among Senegalese people. Patients with oculocutaneous albinism should therefore be evaluated for Hermansky-Pudlak syndrome by mutational screening within the ten HPS genes.