Early-Onset Dementia Associated with a Heterozygous, Nonsense, and de novo Variant in the MBD5 Gene

2021 ◽  
pp. 1-6
Author(s):  
Guillermo González-Ortega ◽  
Sara Llamas-Velasco ◽  
Ana Arteche-López ◽  
Juan Francisco Quesada-Espinosa ◽  
Verónica Puertas-Martín ◽  
...  
Keyword(s):  
Behavioral Problems ◽  
Early Onset ◽  
De Novo ◽  
Clinical Course ◽  
Intellectually Disabled ◽  
Early Onset Dementia ◽  
Domain Protein ◽  
Neurodevelopment Disorders ◽  
De Novo Variant ◽  
Etiologic Study

The haploinsufficiency of the methyl-binding domain protein 5 (MBD5) gene has been identified as the determinant cause of the neuropsychiatric disorders grouped under the name MBD5-neurodevelopment disorders (MAND). MAND includes patients with intellectual disability, behavioral problems, and seizures with a static clinical course. However, a few reports have suggested regression. We describe a non-intellectually disabled female, with previous epilepsy and personality disorder, who developed early-onset dementia. The extensive etiologic study revealed a heterozygous nonsense de novo pathogenic variant in the MBD5 gene. This finding could support including the MBD5 gene in the study of patients with atypical early-onset dementia.

Sporadic progressive myoclonic epilepsy with early‐onset dementia caused by a de novo mutation in PSEN1

2019 ◽  
Vol 7 (5) ◽  
pp. 294-296
Author(s):  
Tomoya Taminato ◽  
Manabu Araki ◽  
Noriko Sato ◽  
Hiroyuki Ishiura ◽  
Jun Mitsui ◽  
...  
Keyword(s):  
Early Onset ◽  
De Novo ◽  
Myoclonic Epilepsy ◽  
De Novo Mutation ◽  
Early Onset Dementia ◽  
Progressive Myoclonic Epilepsy

scholarly journals De novo seven extra repeat expanded mutation in the PRNP gene in an Italian patient with early onset dementia

2007 ◽  
Vol 78 (12) ◽  
pp. 1411-1413 ◽  
Author(s):  
M Cannella ◽  
T Martino ◽  
M Simonelli ◽  
A Ciammola ◽  
R Gradini ◽  
...  
Keyword(s):  
Early Onset ◽  
De Novo ◽  
Prnp Gene ◽  
Italian Patient ◽  
Early Onset Dementia

scholarly journals De novo seven extra repeat expanded mutation in the PRNP gene in an Italian patient with early onset dementia

2009 ◽  
Vol 2009 (jan27 1) ◽  
pp. bcr0820080711-bcr0820080711 ◽  
Author(s):  
M Cannella ◽  
T. Martino ◽  
M. Simonelli ◽  
A. Ciammola ◽  
R. Gradini ◽  
...  
Keyword(s):  
Early Onset ◽  
De Novo ◽  
Prnp Gene ◽  
Italian Patient ◽  
Early Onset Dementia

scholarly journals A novel MBD5 mutation in an intellectually disabled adult female patient with epilepsy: Suggestive of early onset dementia?

2019 ◽  
Vol 7 (8) ◽  
Author(s):  
Willem Verhoeven ◽  
Jos Egger ◽  
Janneke Kipp ◽  
Jiska Verheul‐ aan de Wiel ◽  
Charlotte Ockeloen ◽  
...  
Keyword(s):  
Female Patient ◽  
Adult Female ◽  
Early Onset ◽  
Intellectually Disabled ◽  
Early Onset Dementia ◽  
Adult Female Patient

scholarly journals Pediatric leukemia susceptibility disorders: manifestations and management

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 242-250 ◽  
Author(s):  
Lisa J. McReynolds ◽  
Sharon A. Savage
Keyword(s):  
Early Onset ◽  
Ribosome Biogenesis ◽  
De Novo ◽  
Disease Risk ◽  
Bone Marrow Failure ◽  
Clinical Manifestations ◽  
Cancer Surveillance ◽  
Therapeutic Interventions ◽  
Pediatric Leukemia ◽  
Inherited Susceptibility

Abstract The clinical manifestations of inherited susceptibility to leukemia encompass a wide phenotypic range, including patients with certain congenital anomalies or early-onset myelodysplastic syndrome (MDS) and some with no obvious medical problems until they develop leukemia. Leukemia susceptibility syndromes occur as a result of autosomal dominant, autosomal recessive, or X-linked recessive inheritance, or de novo occurrence, of germline pathogenic variants in DNA repair, ribosome biogenesis, telomere biology, hematopoietic transcription factors, tumor suppressors, and other critical cellular processes. Children and adults with cytopenias, MDS, dysmorphic features, notable infectious histories, immunodeficiency, certain dermatologic findings, lymphedema, unusual sensitivity to radiation or chemotherapy, or acute leukemia with a family history of early-onset cancer, pulmonary fibrosis, or alveolar proteinosis should be thoroughly evaluated for a leukemia susceptibility syndrome. Genetic testing and other diagnostic modalities have improved our ability to identify these patients and to counsel them and their family members for subsequent disease risk, cancer surveillance, and therapeutic interventions. Herein, the leukemia susceptibility syndromes are divided into 3 groups: (1) those associated with an underlying inherited bone marrow failure syndrome, (2) disorders in which MDS precedes leukemia development, and (3) those with a risk primarily of leukemia. Although children are the focus of this review, it is important for clinicians to recognize that inherited susceptibility to cancer can present at any age, even in older adults; genetic counseling is essential and prompt referral to experts in each syndrome is strongly recommended.

De Novo variant in GNB2 associated with neurodevelopmental disease

2021 ◽  
Vol 132 ◽  
pp. S282
Author(s):  
Florencia del Viso ◽  
Lisa Lansdon ◽  
Emily Fleming ◽  
Bonnie Sullivan ◽  
Carol Saunders
Keyword(s):  
De Novo ◽  
Neurodevelopmental Disease ◽  
De Novo Variant

scholarly journals The de novo CACNA1A pathogenic variant Y1384C associated with hemiplegic migraine, early onset cerebellar atrophy and developmental delay leads to a loss of Cav2.1 channel function

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Maria A. Gandini ◽  
Ivana A. Souza ◽  
Laurent Ferron ◽  
A. Micheil Innes ◽  
Gerald W. Zamponi
Keyword(s):  
Developmental Delay ◽  
Early Onset ◽  
Structural Damage ◽  
De Novo ◽  
Splice Variants ◽  
Cerebellar Atrophy ◽  
Familial Hemiplegic Migraine ◽  
Significant Loss ◽  
Loss Of Function ◽  
Hemiplegic Migraine

AbstractCACNA1A pathogenic variants have been linked to several neurological disorders including familial hemiplegic migraine and cerebellar conditions. More recently, de novo variants have been associated with severe early onset developmental encephalopathies. CACNA1A is highly expressed in the central nervous system and encodes the pore-forming CaVα1 subunit of P/Q-type (Cav2.1) calcium channels. We have previously identified a patient with a de novo missense mutation in CACNA1A (p.Y1384C), characterized by hemiplegic migraine, cerebellar atrophy and developmental delay. The mutation is located at the transmembrane S5 segment of the third domain. Functional analysis in two predominant splice variants of the neuronal Cav2.1 channel showed a significant loss of function in current density and changes in gating properties. Moreover, Y1384 variants exhibit differential splice variant-specific effects on recovery from inactivation. Finally, structural analysis revealed structural damage caused by the tyrosine substitution and changes in electrostatic potentials.

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