scholarly journals Donskoy cats as a new model of oculocutaneous albinism with the identification of a splice‐site variant in Hermansky – Pudlak Syndrome 5 gene

2020 ◽  
Vol 33 (6) ◽  
pp. 814-825
Author(s):  
Marina Mériot ◽  
Christophe Hitte ◽  
Maud Rimbault ◽  
Caroline Dufaure de Citres ◽  
Vincent Gache ◽  
...  
Keyword(s):  
Splice Site ◽  
Oculocutaneous Albinism ◽  
New Model ◽  
Hermansky Pudlak Syndrome ◽  
Splice Site Variant

scholarly journals OCA2 splice site variant in German Spitz dogs with oculocutaneous albinism

PLoS ONE ◽  
2017 ◽  
Vol 12 (10) ◽  
pp. e0185944 ◽  
Author(s):  
Madleina Caduff ◽  
Anina Bauer ◽  
Vidhya Jagannathan ◽  
Tosso Leeb
Keyword(s):  
Splice Site ◽  
Oculocutaneous Albinism ◽  
Splice Site Variant

scholarly journals A rare large duplication of MLH1 identified in Lynch syndrome

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Abhishek Kumar ◽  
Nagarajan Paramasivam ◽  
Obul Reddy Bandapalli ◽  
Matthias Schlesner ◽  
Tianhui Chen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Lynch Syndrome ◽  
Splice Site ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Splice Donor Site ◽  
Laboratory Diagnostics ◽  
Mmr Genes ◽  
Base Pair Deletion ◽  
Splice Site Variant

Abstract Background The most frequently identified strong cancer predisposition mutations for colorectal cancer (CRC) are those in the mismatch repair (MMR) genes in Lynch syndrome. Laboratory diagnostics include testing tumors for immunohistochemical staining (IHC) of the Lynch syndrome-associated DNA MMR proteins and/or for microsatellite instability (MSI) followed by sequencing or other techniques, such as denaturing high performance liquid chromatography (DHPLC), to identify the mutation. Methods In an ongoing project focusing on finding Mendelian cancer syndromes we applied whole-exome/whole-genome sequencing (WES/WGS) to 19 CRC families. Results Three families were identified with a pathogenic/likely pathogenic germline variant in a MMR gene that had previously tested negative in DHPLC gene variant screening. All families had a history of CRC in several family members across multiple generations. Tumor analysis showed loss of the MMR protein IHC staining corresponding to the mutated genes, as well as MSI. In family A, a structural variant, a duplication of exons 4 to 13, was identified in MLH1. The duplication was predicted to lead to a frameshift at amino acid 520 and a premature stop codon at amino acid 539. In family B, a 1 base pair deletion was found in MLH1, resulting in a frameshift and a stop codon at amino acid 491. In family C, we identified a splice site variant in MSH2, which was predicted to lead loss of a splice donor site. Conclusions We identified altogether three pathogenic/likely pathogenic variants in the MMR genes in three of the 19 sequenced families. The MLH1 variants, a duplication of exons 4 to 13 and a frameshift variant, were novel, based on the InSiGHT and ClinVar databases; the MSH2 splice site variant was reported by a single submitter in ClinVar. As a variant class, duplications have rarely been reported in the MMR gene literature, particularly those covering several exons.

A common founder effect of the splice site variant c.-23 + 1G > A in GJB2 gene causing autosomal recessive deafness 1A (DFNB1A) in Eurasia

2021 ◽  
Author(s):  
Aisen V. Solovyev ◽  
Alena Kushniarevich ◽  
Elena Bliznetz ◽  
Marita Bady-Khoo ◽  
Maria R. Lalayants ◽  
...  
Keyword(s):  
Splice Site ◽  
Founder Effect ◽  
Autosomal Recessive ◽  
Gjb2 Gene ◽  
C 23 ◽  
Common Founder ◽  
Splice Site Variant

A splice-site variant in ANKRD11 associated with classical KBG syndrome

2017 ◽  
Vol 173 (10) ◽  
pp. 2844-2846 ◽  
Author(s):  
Karen J. Low ◽  
Alison Hills ◽  
Maggie Williams ◽  
Celia Duff-Farrier ◽  
Shane McKee ◽  
...  
Keyword(s):  
Splice Site ◽  
Kbg Syndrome ◽  
Splice Site Variant

scholarly journals A splice site variant in INPP5E causes diffuse cystic renal dysplasia and hepatic fibrosis in dogs

PLoS ONE ◽  
2018 ◽  
Vol 13 (9) ◽  
pp. e0204073 ◽  
Author(s):  
Kati J. Dillard ◽  
Marjo K. Hytönen ◽  
Daniel Fischer ◽  
Kimmo Tanhuanpää ◽  
Mari S. Lehti ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
Splice Site ◽  
Renal Dysplasia ◽  
Cystic Renal Dysplasia ◽  
Splice Site Variant

scholarly journals Hermansky-Pudlak Syndrome and Lung Disease: Pathogenesis and Therapeutics

2021 ◽  
Vol 12 ◽  
Author(s):  
Pamela Velázquez-Díaz ◽  
Erika Nakajima ◽  
Parand Sorkhdini ◽  
Ashley Hernandez-Gutierrez ◽  
Adam Eberle ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Molecular Mechanisms ◽  
Management Strategies ◽  
Oculocutaneous Albinism ◽  
Alveolar Epithelial Cells ◽  
Multisystem Disorder ◽  
Alveolar Epithelial ◽  
Novel Treatments ◽  
Molecular Approaches ◽  
Hermansky Pudlak Syndrome

Hermansky-Pudlak Syndrome (HPS) is a rare, genetic, multisystem disorder characterized by oculocutaneous albinism (OCA), bleeding diathesis, immunodeficiency, granulomatous colitis, and pulmonary fibrosis. HPS pulmonary fibrosis (HPS-PF) occurs in 100% of patients with subtype HPS-1 and has a similar presentation to idiopathic pulmonary fibrosis. Upon onset, individuals with HPS-PF have approximately 3 years before experiencing signs of respiratory failure and eventual death. This review aims to summarize current research on HPS along with its associated pulmonary fibrosis and its implications for the development of novel treatments. We will discuss the genetic basis of the disease, its epidemiology, and current therapeutic and clinical management strategies. We continue to review the cellular processes leading to the development of HPS-PF in alveolar epithelial cells, lymphocytes, mast cells, and fibrocytes, along with the molecular mechanisms that contribute to its pathogenesis and may be targeted in the treatment of HPS-PF. Finally, we will discuss emerging new cellular and molecular approaches for studying HPS, including lentiviral-mediated gene transfer, induced pluripotent stem cells (iPSCs), organoid and 3D-modelling, and CRISPR/Cas9-based gene editing approaches.

Fluoropyrimidine toxicity in patients with dihydropyrimidine dehydrogenase splice site variant: the need for further revision of dose and schedule

2013 ◽  
Vol 8 (5) ◽  
pp. 417-423 ◽  
Author(s):  
Elena Magnani ◽  
Enrico Farnetti ◽  
Davide Nicoli ◽  
Bruno Casali ◽  
Luisa Savoldi ◽  
...  
Keyword(s):  
Splice Site ◽  
Dihydropyrimidine Dehydrogenase ◽  
Splice Site Variant

A Rare Case of Hermansky-Pudlak Syndrome Involving Bilateral Lung: Histopathologic and Electron Microscopic Findings

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S42-S43
Author(s):  
Atreyee Basu ◽  
Surya Seshan ◽  
Luis Angel ◽  
Andre Moreira ◽  
Fang Zhou
Keyword(s):  
Alveolar Macrophages ◽  
Lamellar Body ◽  
Oculocutaneous Albinism ◽  
Electron Microscopic ◽  
Restrictive Lung Disease ◽  
Breath Sounds ◽  
Membrane Bound ◽  
Hermansky Pudlak Syndrome ◽  
Bilateral Lung ◽  
End Stage

Abstract Introduction Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive hereditary disorder characterized by oculocutaneous albinism and bleeding diathesis. Transplantation is often conducted to treat lung fibrosis, which is the most fatal complication of this disease. While the literature discusses the diagnosis of HPS based on genetic testing, radiology, and electron microscopic (EM) findings of platelet granules, there is a paucity of images in the literature illustrating the pulmonary histopathologic and EM features of HPS. Case Report Here we present striking histopathologic and EM images from a case of pulmonary fibrosis due to HPS in a 48-year-old female. The patient presented with restrictive lung disease and bilateral decreased breath sounds with diffuse crackles. She was clinically diagnosed with HPS and underwent bilateral lung transplant. On histopathology, both pneumonectomy specimens showed diffuse interstitial fibrosing and cellular pneumonitis with end-stage remodeling and type II pneumocyte (PC-II) hyperplasia. The PC-IIs had abundant foamy cytoplasm and compressed scalloped nuclei. Alveolar macrophages contained fine brown granules positive for PAS-D stain. EM analysis revealed that the PC-IIs contained numerous lamellated myelin bodies (so-called giant lamellar body degeneration) suggestive of surfactant admixed with lipid and luminal microvilli. The pigmented alveolar macrophages also contained lamellated myelin bodies, as well as clusters of single membrane-bound structures with varying size and electron density admixed with vacuolar and granular debris suggestive of ceroid deposits. Conclusion Based on light microscopy, histochemical analysis, EM, and clinical presentation, it was concluded that our findings were consistent with pulmonary changes as seen in HPS.

Hermansky–Pudlak Syndrome

2020 ◽  
Vol 41 (02) ◽  
pp. 238-246
Author(s):  
Wilfredo De Jesus Rojas ◽  
Lisa R. Young
Keyword(s):  
Protein Trafficking ◽  
Health Management ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Oculocutaneous Albinism ◽  
Clinical Approach ◽  
Recessive Mutations ◽  
Hermansky Pudlak Syndrome ◽  
Traction Bronchiectasis

AbstractHermansky–Pudlak syndrome (HPS) is a multisystemic autosomal recessive disorder characterized by oculocutaneous albinism, bleeding diathesis, and lethal pulmonary fibrosis (PF) in some HPS subtypes. During middle adulthood, ground-glass opacities, reticulation, and traction bronchiectasis develop with progression of PF. HPS is an orphan disease occurring in 1 in 500,000 to 1,000,000 individuals worldwide, though the prevalence is 1 in 1,800 in individuals with Puerto Rican heritage. Recessive mutations or disruptions in HPS genes alter the function of HPS proteins which are components of biogenesis of lysosome-related organelle complexes and are critical for intracellular protein trafficking. Diagnosis and management of HPS-related comorbidities represent a challenge to physicians, and a multidisciplinary clinical approach is necessary for early detection, health management, and surveillance of PF in patients with HPS types 1, 2, and 4. Treatment options for individuals with HPS-PF include pirfenidone and lung transplantation. In this article, we describe the epidemiology, genetics, clinical manifestations, and management of HPS.

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