Griscelli syndrome types 1 and 2.

The American Journal of Human Genetics (Impact Factor: 10.99). 12/2002; 71(5):1237-8; author reply 1238. DOI: 10.1086/344140
Source: PubMed
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    ABSTRACT: This review focuses on recent studies implicating class V myosins in organelle and macromolecule transport within neurons. These studies reveal that class V myosins play important roles in a wide range of fundamental processes occurring within neurons, including the transport into dendritic spines of organelles that support synaptic plasticity, the establishment of neuronal shape, the specification of polarized cargo transport, and the subcellular localization of mRNA.
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    ABSTRACT: Clonal natural killer (NK) and T cell expansions induced by Epstein- Barr virus (EBV) and genetic alterations compromising NK cell killing are the most common causes of hemophagocytic lymphohistocytosis (HLH). Generally, HLH is induced by an immune dysfunction where hypercytokinemia develops into reactive hemophagocytosis. In this work we review the causes of HLH and describe a case of a monoclonal expansion of EBV-negative NK cells associated to HLH in a seventeen-month-old girl suffering of Griscelli syndrome type-2 with novel RAB27A mutation and showing partial albinism, persistent fever, hepatosplenomegaly, adenopaties and cytopenias. At diagnosis, no evidence of active viral infections, including EBV, was found. Expansion of NK cells (5300/μl in peripheral blood) CD2+CD7+CD8+CD16+CD56+CD94+CD158a/h+CD158b/j–Perforin+ Granzyme B+ was found. After treatment (HLH-2004 protocol: Cyclosporin, Etoposide and Dexamethasone), NK cell count fell to 850/μl and progressively increased to pre-therapy levels by week 28. X-chromosome inactivation assay demonstrated NK cell monoclonality. NK cells sustained a strong killing and secreted high amounts of IFN-γ. At diagnosis, serum levels of sIL-2R (36,8 ng/ml) and IFN-γ (400 pg/ml) were elevated. In conclusion, we describe a monoclonal expansion of EBV-negative NK cells highly secretory of IFN-γ as the most probable cause of HLH episode in a patient with Griscelli syndrome type-2. NK cell count recovered normal levels and phenotype after bone marrow transplantation from her HLA identical sister.ResumenLas causas más comunes de linfohistiocitosis hemofagocítica (HLH) son expansiones clonales de células NK y T, inducidas por EBV, así como las alteraciones genéticas que comprometen la actividad asesina de las NKs. Generalmente, HLH se desencadena por una disfunción inmune en la que se desarrolla hipercitoquinemia. En este trabajo se resumen las causas más comunes de HLH y se presenta un caso en el que una expansión monoclonal de células NK, EBV-negativas, se asocia a HLH en una paciente aquejada de Síndrome de Griscelli tipo-2 (GS2). Se trata de una niña de 17 meses con una mutación de nueva descripción en RAB27A, con albinismo parcial, fiebre persistente, hepatoesplenomegalia, adenopatías y citopenias al diagnóstico. No se detectaron evidencias de infecciones virales activas, incluida EBV. Se detectó una expansión de células NKs (5300/μl) CD2+CD7+CD8+CD16+CD56+ CD94+CD158a/h+CD158b/j–Perforin+Granzyme-B+. Tras el tratamiento (Protocolo HLH-2004: Cyclosporina, Etoposido y Dexametasona), la cifra de células NK se redujo a 850/μl y que aumentaron progresivamente hasta alcanzar niveles similares al diagnóstico. El ensayo de inactivación del cromosoma X demostró monoclonalidad de células NK. Dichas células mantenían intacta su actividad asesina y secretaban grandes cantidades de IFN-γ. Al diagnóstico los niveles séricos de sIL-2R (36.8 ng/ml) e IFN-γ (400 pg/ml) estaban elevados. En conclusión, se describe un caso de una expansión monoclonal de células NK, EBV-negativas, que secretan grandes cantidades de IFN-γ como la causa más probable del episodio de HLH en una paciente con GS2. Tras el trasplante de médula ósea de su hermana HLA-idéntica, las cifras y el fenotipo de las células NK recobraron la normalidad.
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    ABSTRACT: Griscelli syndrome (GS) (MIM 214450) is a rare au- tosomal recessive genetic disorder characterized by partial albinism with silvery gray hair, recurrent in- fections, cellular immunodeficiency and neurologi- cal abnormalities. Acute disseminated encephalom- yelitis (ADEM) is a monophasic, immune-mediated disorder that produces multifocal demyelinating le- sions within the central nervous system. We report a three years and six months old girl patient with GS who presented ADEM. GS was diagnosed when she was six months old. She was admitted to hospi- tal because of ataxia, gait disturbance and somno- lence for four days. The physical examination reve- aled hyperreactive deep tendon reflexes, lower limb power was grade 3/5, bilaterally positive Achilles' clonus and Babinsky's sign. Laboratory investigati- ons including complete blood cell count, serum bi- ochemistry analysis, fibrinogen level and bone marrow examination were all within normal limits. The cerebrospinal fluid showed no pleocytosis with increased protein level. Brain and spinal magnetic resonance imaging (MRI) revealed multifocal ab- normal high-signal intensity mainly in the white matter of the cerebellum, brainstem and spinal cord as well as in the cerebrum. The typical MRI ÖZET


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