Primary immunodeficiency associated with hypopigmentation: A differential diagnosis approach

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.

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Development, characterization, and hematopoietic differentiation of Griscelli syndrome type 2 induced pluripotent stem cells

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02364-z ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Gülen Güney-Esken ◽

Özgür Doğuş Erol ◽

Burcu Pervin ◽

Gülben Gürhan Sevinç ◽

Tamer Önder ◽

...

Keyword(s):

Stem Cells ◽

Pluripotent Stem Cells ◽

Treatment Options ◽

Syndrome Type ◽

Rt Pcr ◽

Novel Treatment ◽

Griscelli Syndrome ◽

Induced Pluripotent

Abstract Background Griscelli syndrome type 2 (GS-2) is a rare, autosomal recessive immune deficiency syndrome caused by a mutation in the RAB27A gene, which results in the absence of a protein involved in vesicle trafficking and consequent loss of function of in particular cytotoxic T and NK cells. Induced pluripotent stem cells (iPSC) express genes associated with pluripotency, have the capacity for infinite expansion, and can differentiate into cells from all three germ layers. They can be induced using integrative or non-integrative systems for transfer of the Oct4, Sox2, Klf4, and cMyc (OSKM) transcription factors. To better understand the pathophysiology of GS-2 and to test novel treatment options, there is a need for an in vitro model of GS-2. Methods Here, we generated iPSCs from 3 different GS-2 patients using lentiviral vectors. The iPSCs were characterized using flow cytometry and RT-PCR and tested for the expression of pluripotency markers. In vivo differentiation to cells from all three germlines was tested using a teratoma assay. In vitro differentiation of GS-2 iPSCs into hematopoietic stem and progenitor cells was done using Op9 feeder layers and specified media. Results All GS-2 iPSC clones displayed a normal karyotype (46XX or 46XY) and were shown to express the same RAB27A gene mutation that was present in the original somatic donor cells. GS-2 iPSCs expressed SSEA1, SSEA4, TRA-1-60, TRA-1-81, and OCT4 proteins, and SOX2, NANOG, and OCT4 expression were confirmed by RT-PCR. Differentiation capacity into cells from all three germ layers was confirmed using the teratoma assay. GS-2 iPSCs showed the capacity to differentiate into cells of the hematopoietic lineage. Conclusions Using the lentiviral transfer of OSKM, we were able to generate different iPSC clones from 3 GS-2 patients. These cells can be used in future studies for the development of novel treatment options and to study the pathophysiology of GS-2 disease.

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