An allelic variant of Griscelli disease: presentation with severe hypotonia, mental-motor retardation, and hypopigmentation consistent with Elejalde syndrome (neuroectodermal melanolysosomal disorder)

Sanal, Özden; L, Yel; Küçükali, T.; Gilbert-Barnes, E; Tardieu, Marc; Texcan, I; Ersoy, F; Metìn, Ayşe; Basile, Geneviève de Saint

doi:10.1007/s004150070162

Cited by 40 publications

(30 citation statements)

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“…Thus, no gross alteration of cerebellar architecture was found in d-n mice during postnatal development or adulthood. Nevertheless, the smaller size of the cerebellum in these mice is consistent with that of GS1 and ES patients (Sanal et al, 2000(Sanal et al, , 2002.…”

Section: Neurological Phenotypes Of D-n Micesupporting

confidence: 71%

“…Our results implied that myosin Va is important for the extension of SER into PC spines and is involved in synaptic plasticity of the cerebellum. This finding might partially account for the disease background of GS1 and ES patients who show ataxic cerebellar movement and cerebellar atrophy (Sanal et al, 2000(Sanal et al, , 2002Ivanovich et al, 2001). However, they are still insufficient to understand all of the pathological processes of this neurological defect.…”

Section: Introductionmentioning

confidence: 99%

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A Role for Myosin Va in Cerebellar Plasticity and Motor Learning: A Possible Mechanism Underlying Neurological Disorder in Myosin Va Disease

Miyata

Kishimoto²,

Tanaka³

et al. 2011

J. Neurosci.

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Mutations of the myosin Va gene cause the neurological diseases Griscelli syndrome type 1 and Elejalde syndrome in humans and dilute phenotypes in rodents. To understand the pathophysiological mechanisms underlying the neurological disorders in myosin Va diseases, we conducted an integrated analysis at the molecular, cellular, electrophysiological, and behavioral levels using the dilute-neurological (d-n) mouse mutant. These mice manifest an ataxic gait and clonic seizures during postnatal development, but the neurological disorders are ameliorated in adulthood. We found that smooth endoplasmic reticulum (SER) rarely extended into the dendritic spines of Purkinje cells (PCs) of young d-n mice, and there were few, if any, IP 3 receptors. Moreover, long-term depression (LTD) at parallel fiber-PC synapses was abolished, consistent with our previous observations in juvenile lethal dilute mutants.

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Section: Neurological Phenotypes Of D-n Micesupporting

confidence: 71%

Section: Introductionmentioning

confidence: 99%

A Role for Myosin Va in Cerebellar Plasticity and Motor Learning: A Possible Mechanism Underlying Neurological Disorder in Myosin Va Disease

Miyata

Kishimoto²,

Tanaka³

et al. 2011

J. Neurosci.

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“…Subsequently, FLAIR-MRI of the brain might also be helpful in the interpretation of the degree of neurological defects. Primary neurological deficiency marked by profound, congenital cerebellar atrophy is associated to GS1 (Elejalde) (27), and secondary neurological damage involving the white matter, due to leukocyte infiltration that occurs during HLH manifestation, is associated with GS2 and CHS. Finally, sequencing the candidate gene is mandatory to identify the molecular basis of the disease, supporting physicians to adopt effective treatment, which is available for GS2 and CHS patients as BMT.…”

Section: Discussionmentioning

confidence: 99%

Griscelli syndrome-type 2 in twin siblings: case report and update on RAB27A human mutations and gene structure

Meschede

Santos

Izidoro-Toledo

et al. 2008

Braz J Med Biol Res

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Griscelli syndrome (GS) is a rare autosomal recessive disorder caused by mutation in the MYO5A (GS1, Elejalde), RAB27A (GS2) or MLPH (GS3) genes. Typical features of all three subtypes of this disease include pigmentary dilution of the hair and skin and silvery-gray hair. Whereas the GS3 phenotype is restricted to the pigmentation dysfunction, GS1 patients also show primary neurological impairment and GS2 patients have severe immunological deficiencies that lead to recurrent infections and hemophagocytic syndrome. We report here the diagnosis of GS2 in 3-year-old twin siblings, with silvery-gray hair, immunodeficiency, hepatosplenomegaly and secondary severe neurological symptoms that culminated in multiple organ failure and death. Light microscopy examination of the hair showed large, irregular clumps of pigments characteristic of GS. A homozygous nonsense mutation, C-T transition (c.550C>T), in the coding region of the RAB27A gene, which leads to a premature stop codon and prediction of a truncated protein (R184X), was found. In patient mononuclear cells, RAB27A mRNA levels were the same as in cells from the parents, but no protein was detected. In addition to the case report, we also present an updated summary on the exon/intron organization of the human RAB27A gene, a literature review of GS2 cases, and a complete list of the human mutations currently reported in this gene. Finally, we propose a flow chart to guide the early diagnosis of the GS subtypes and Chédiak-Higashi syndrome.

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“…GS type 1 is caused by a mutation in the myosin Va (MYO5A) gene located on chromosome 15q21, which regulates organelle transport in both melanocytes and neuronal cells. 3,4 The outcome is guarded as it depends on the severity of neurological manifestations. GS type 3 is caused by mutation in the gene located on chromosome 2q37.3.…”

Section: Introductionmentioning

confidence: 99%

Hematopoietic SCT in children with Griscelli syndrome: a single-center experience

Al-Ahmari

Al-Ghonaium

Al-mansoori

et al. 2010

Bone Marrow Transplant

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In total, 11 consecutive pediatric patients with Griscelli syndrome (GS) type 2, who received allogeneic hematopoietic SCT (aHSCT) at our center between 1993 and 2007, were reviewed. The median age at transplantation was 8.2 months (range, 4-36.3 months) and the median time from diagnosis to transplantation was 3.7 months (range, 1.4-19.5 months). Seven patients developed an accelerated phase and were treated with chemotherapy before transplantation. At the time of transplantation, all patients were in clinical remission. The source of grafts was matched-related marrows in eight patients and partially mismatched unrelated cords in three patients. All patients were engrafted at a median time of 15 days (range, 12-36 days). Grade I-II acute GVHD and venoocclusive disease occurred in three and one patient, respectively. A total of 10 patients are now alive and disease free at a median of 4.8 years post-HSCT. The post transplant course was complicated by CMV infection in four patients. One patient died in remission from septic shock, 6 months after transplantation. Chimerism studies at the last contact are available for nine patients: six patients have complete donor chimerism and three have stable mixed chimerism. Early aHSCT from matchedrelated donors or unrelated cord blood for children with GS is feasible.

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An allelic variant of Griscelli disease: presentation with severe hypotonia, mental-motor retardation, and hypopigmentation consistent with Elejalde syndrome (neuroectodermal melanolysosomal disorder)

Cited by 40 publications

References 0 publications

A Role for Myosin Va in Cerebellar Plasticity and Motor Learning: A Possible Mechanism Underlying Neurological Disorder in Myosin Va Disease

A Role for Myosin Va in Cerebellar Plasticity and Motor Learning: A Possible Mechanism Underlying Neurological Disorder in Myosin Va Disease

Griscelli syndrome-type 2 in twin siblings: case report and update on RAB27A human mutations and gene structure

Hematopoietic SCT in children with Griscelli syndrome: a single-center experience

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