Primary immunodeficiency associated with hypopigmentation: A differential diagnosis approach

Abstract

Primary immunodeficiency diseases (PIDs) are a group of more than 400 disorders representing aberrant functioning or development of immune system. Hypopigmentation syndromes also characterize a distinguished cluster of diseases. However, hypopigmentation may also signify a feature of genetic diseases associated with immunodeficiency, such as Chediak–Higashi syndrome, Griscelli syndrome type 2, Hermansky–Pudlak syndrome type 2 and type 10, Vici syndrome, and P14/LAMTOR2 deficiency, all of which are linked with dysfunction in vesicular/endosomal trafficking. Regarding the highly overlapping features, these disorders need a comprehensive examination for prompt diagnosis and effective management. As an aid to clinician, distinguishing the pathophysiology, clinical phenotype, and diagnosis as well as treatment options of the six mentioned PID disorders associated with hypopigmentation are described and discussed in this review.

Co-expression analysis to identify key modules and hub genes associated with COVID-19 in platelets

“…It is noteworthy that LAMTOR2 is a known regulator of the MAPK/ERK and mTOR signaling pathways [ 56 , 57 ], both of which were shown to be important in regulating platelet function [ 58 , 59 ]. Moreover, the p14/LAMTOR2 deficiency- which is associated with one of the primary immunodeficiency diseases that also include “Hermansky–Pudlak syndrome type 2”- has been linked to platelet defects [ 60 ]. However, more needs to be done to examine the exact role of LAMTOR2 in platelets of COVID-19 patients.…”

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“…The RAB27A gene encodes the Rab27a protein and is important for vesicle transport and docking in a variety of cell types (platelets, leukocytes and melanocytes). Variants in RAB27A lead to GS2, resulting in an immune dysregulatory phenotype with increased susceptibility to infection, cytopenias, HLH, neurologic involvement and complete to partial albinism [2]. Lack of pigment and immunodeficiency in GS2 are linked as both result from a dysfunction in secretory vesicles, a component essential for the proper functioning of cytotoxic T lymphocytes, natural killer cells and melanocytes.…”

“…Griscelli Syndrome Type 2 (GS2) is a rare autosomal recessive disease characterized by organ granulomas, central nervous system inflammation, hemophagocytic lymphohistiocytosis (HLH) and partial albinism. Patients have immune dysregulation secondary to dysfunctions in natural killer (NK) cell and T cell cytotoxicity as a result of poor vesicular transport [1][2]. Typically, patients also have abnormal skin and hair pigmentation from accumulation of melanosome clumps in hair shafts and melanocytes.…”

Co-expression analysis to identify key modules and hub genes associated with COVID19 in Platelets

“…It is noteworthy that LAMTOR2 is a known regulator of the MAPK/Erk and mTor signaling pathways 49,50 , both of which are shown to be important in regulating platelet function 51,52 . Moreover, the p14/LAMTOR2 deficiency-which is associated with one of the primary immunodeficiency diseases that also include "Hermansky-Pudlak syndrome type 2"-has been linked to platelet defects 53 . However, more needs to be done to examine the exact role of LAMTOR2 in platelets of COVID19 patients.…”