scholarly journals Case report of a de novo mutation of PCDH19 in Saudi family limited to females

2022 ◽  
Vol 5 (1) ◽  
pp. 01-04
Author(s):  
Rawan Alsheikh ◽  
Amal Al-Qassmi
Keyword(s):  
De Novo ◽  
Somatic Mosaicism ◽  
Febrile Illness ◽  
Autistic Traits ◽  
De Novo Mutation ◽  
Epilepsy Syndrome ◽  
Childhood Onset ◽  
Behavioral Abnormalities ◽  
Nucleotide Mutation ◽  
Saudi Family

Up to date more than 60 different mutations in PCDH19 have been identified. Most of PCDH19 gene is located in Xq22 and produces nonclustered delta protocadherin. This disorder primarily manifests in heterozygote females due to random X chromosome inactivation leading to somatic mosaicism and abnormal cellular interference between cells with and without delta-protocadherin., but we a heterozygous nucleotide mutation causing amino acid 561 to change from Pro to Ser (p.Pro561Ser). This mutation was de novo, and this alteration was not found in her parents. PCDH19-related epilepsy is a distinct childhood-onset epilepsy syndrome characterized by brief clusters of febrile and afebrile seizures with onset primarily before the age of three years, cognitive impairment, autistic traits, and behavioral abnormalities. We describe the features of a de novo mutation in 3 sibling, presented with early onset of seizure, two of them were controlled and wean off medication was at age of six year and her sister at age of 10 year .The youngest sister still partially controlled on medication, she had seizure only during febrile illness.

scholarly journals Case Report of a de Novo Mutation of PCDH19 in Saudi Family Limited to Females

2021 ◽  
Vol 6 (12) ◽  
pp. 940-943
Author(s):  
Rawan Alsheikh, MD ◽  
Amal Al-Qassmi, MD
Keyword(s):  
De Novo ◽  
Somatic Mosaicism ◽  
Febrile Illness ◽  
Autistic Traits ◽  
De Novo Mutation ◽  
Epilepsy Syndrome ◽  
Childhood Onset ◽  
Behavioral Abnormalities ◽  
Nucleotide Mutation ◽  
Saudi Family

Up to date more than 60 different mutations in PCDH19 have been identified. Most of PCDH19 gene is located in Xq22 and produces nonclustered delta protocadherin. This disorder primarily manifests in heterozygote females due to random X chromosome inactivation leading to somatic mosaicism and abnormal cellular interference between cells with and without delta-protocadherin., but we a heterozygous nucleotide mutation causing amino acid 561 to change from Pro to Ser (p.Pro561Ser). This mutation was de novo, and this alteration was not found in her parents. PCDH19-related epilepsy is a distinct childhood-onset epilepsy syndrome characterized by brief clusters of febrile and afebrile seizures with onset primarily before the age of three years, cognitive impairment, autistic traits, and behavioral abnormalities. We describe the features of a de novo mutation in 3 sibling, presented with early onset of seizure, two of them were controlled and wean off medication was at age of six year and her sister at age of 10 year .The youngest sister still partially controlled on medication, she had seizure only during febrile illness.

Sleep Exacerbations and Facial Twitching: Diagnostic Clues for ADCY5-Related Dyskinesias

2020 ◽  
Author(s):  
Margherita Nosadini ◽  
Gianluca D'Onofrio ◽  
Maria Federica Pelizza ◽  
Concetta Luisi ◽  
Davide Padrin ◽  
...  
Keyword(s):  
Movement Disorder ◽  
Developmental Delay ◽  
De Novo ◽  
Brain Magnetic Resonance Imaging ◽  
Neurological Impairment ◽  
De Novo Mutation ◽  
Oligoclonal Bands ◽  
Emotional Stimuli ◽  
Childhood Onset ◽  
Ataxic Gait

Abstract Background Mutations in the adenylate cyclase 5 (ADCY5) gene are associated with childhood-onset paroxysmal dyskinesia. Methods We report a new video-documented case of pediatric ADCY5-related dyskinesia with de novo ADCY5 mutation. Results A boy born to nonconsanguineous parents after an uneventful pregnancy had developmental delay and hypotonia. At the age of 7 months, he presented with paroxysmal jerky–choreic–dystonic involuntary movements in wakefulness involving limbs, trunk, and face, exacerbated by emotional stimuli. These episodes gradually worsened in duration and frequency: at the age of 2.5 years, they occurred up to six times per day, and appeared also during sleep in prolonged bouts; the boy also had basal choreoathetoid–dystonic movements, hyperactivity, paraparetic–ataxic gait, generalized hypotonia with brisk tendon reflexes, drooling, and language delay with intellectual disability. Brain magnetic resonance imaging, electroencephalogram, electromyogram, eye review, metabolic investigations, oligoclonal bands, and autoantibodies were normal. Extensive genetic testing had not let to a diagnosis, until a heterozygous de novo mutation c.1252C > T (p.Arg418Trp) was identified in the ADCY5 gene. Clonazepam had partial effectiveness. The boy walked at the age of 3.5 years. At the age of 5 years, the paroxysmal movement disorder has slightly improved. Conclusion ADCY5 mutations should be considered among the differential diagnoses of early-onset paroxysmal choreic–athetosic–myoclonic–dystonic movement disorder involving limbs, trunk, and face, in patients with global neurological impairment with hypotonia and developmental delay. Facial dyskinesias and exacerbation by drowsiness/sleep and emotional stimuli are important clues that may allow a timely recognition of the disorder and avoidance of unnecessary diagnostic investigations.

De novo factor VIII gene intron 22 inversion in a female carrier presents as a somatic mosaicism

Blood ◽  
2000 ◽  
Vol 96 (8) ◽  
pp. 2905-2906 ◽  
Author(s):  
Johannes Oldenburg ◽  
Simone Rost ◽  
Osman El-Maarri ◽  
Marco Leuer ◽  
Klaus Olek ◽  
...  
Keyword(s):  
Germ Cells ◽  
De Novo ◽  
Somatic Mosaicism ◽  
Mitotic Cell ◽  
De Novo Mutation ◽  
Female Carrier ◽  
Meiotic Cell ◽  
Cell Divisions ◽  
Intron 22 Inversion ◽  
Bivalent Formation

The intron 22 inversion represents the most prevalentfactor VIII gene defect in severe hemophilia A, accounting for about 40% of all mutations. It is hypothesized that the inversion mutations occur almost exclusively in germ cells during meiotic cell division by intrachromosomal recombination between 1 of 2 telomeric copies of the Int22h region and its intragenic homologue. The majority of inversion mutations originate in male germ cells, where the lack of bivalent formation may facilitate flipping of the telomeric end of the single X chromosome. This is the first intron 22 inversion that presents as a somatic mosaicism in a female, affecting only about 50% of lymphocyte and fibroblast cells of the proposita. Supposing a post-zygotic de novo mutation as the usual cause of somatic mosaicism, the finding would imply that the intron 22 inversion mutation is not restricted to meiotic cell divisions but can also occur during mitotic cell divisions, either in germ cell precursors or in somatic cells.

scholarly journals A novel de novo mutation inATP1A3and childhood-onset schizophrenia

2016 ◽  
Vol 2 (5) ◽  
pp. a001008 ◽  
Author(s):  
Niklas Smedemark-Margulies ◽  
Catherine A. Brownstein ◽  
Sigella Vargas ◽  
Sahil K. Tembulkar ◽  
Meghan C. Towne ◽  
...  
Keyword(s):  
De Novo ◽  
De Novo Mutation ◽  
Childhood Onset ◽  
Childhood Onset Schizophrenia

scholarly journals De novo mutation and somatic mosaicism of gene mutation in type 2A, 2B and 2M VWD

2016 ◽  
Vol 14 (S1) ◽  
Author(s):  
Ming-Ching Shen ◽  
Ming Chen ◽  
Gwo-Chin Ma ◽  
Shun-Ping Chang ◽  
Ching-Yeh Lin ◽  
...  
Keyword(s):  
Gene Mutation ◽  
De Novo ◽  
Somatic Mosaicism ◽  
De Novo Mutation

scholarly journals Identical de novo  Mutation in the Type 1 Ryanodine Receptor Gene Associated with Fatal, Stress-induced Malignant Hyperthermia in Two Unrelated Families

2011 ◽  
Vol 115 (5) ◽  
pp. 938-945 ◽  
Author(s):  
Linda Groom ◽  
Sheila M. Muldoon ◽  
Zhen Zhi Tang ◽  
Barbara W. Brandom ◽  
Munkhuu Bayarsaikhan ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
De Novo ◽  
Receptor Gene ◽  
Febrile Illness ◽  
De Novo Mutation ◽  
Heat Sensitivity ◽  
Wild Type ◽  
In Cis

Background Mutations in the type 1 ryanodine receptor gene (RYR1) result in malignant hyperthermia, a pharmacogenetic disorder typically triggered by administration of anesthetics. However, cases of sudden death during exertion, heat challenge, and febrile illness in the absence of triggering drugs have been reported. The underlying causes of such drug-free fatal "awake" episodes are unknown. Methods De novo R3983C variant in RYR1 was identified in two unrelated children who experienced fatal, nonanesthetic awake episodes associated with febrile illness and heat stress. One of the children also had a second novel, maternally inherited D4505H variant located on a separate haplotype. Effects of all possible heterotypic expression conditions on RYR1 sensitivity to caffeine-induced Ca release were determined in expressing RYR1-null myotubes. Results Compared with wild-type RYR1 alone (EC50 = 2.85 ± 0.49 mM), average (± SEM) caffeine sensitivity of Ca release was modestly increased after coexpression with either R3983C (EC50 = 2.00 ± 0.39 mM) or D4505H (EC50 = 1.64 ± 0.24 mM). Remarkably, coexpression of wild-type RYR1 with the double mutant in cis (R3983C-D4505H) produced a significantly stronger sensitization of caffeine-induced Ca release (EC50 = 0.64 ± 0.17 mM) compared with that observed after coexpression of the two variants on separate subunits (EC50 = 1.53 ± 0.18 mM). Conclusions The R3983C mutation potentiates D4505H-mediated sensitization of caffeine-induced RYR1 Ca release when the mutations are in cis (on the same subunit) but not when present on separate subunits. Nevertheless, coexpression of the two variants on separate subunits still resulted in a ∼2-fold increase in caffeine sensitivity, consistent with the observed awake episodes and heat sensitivity.

scholarly journals De novo mutation in MEN1 is not associated with parental somatic mosaicism

2017 ◽  
Vol 24 (1) ◽  
pp. L1-L3 ◽  
Author(s):  
Yael Laitman ◽  
Anat Jaffe ◽  
Hagit Schayek ◽  
Eitan Friedman
Keyword(s):  
De Novo ◽  
Somatic Mosaicism ◽  
De Novo Mutation

scholarly journals De novo mutation screening in childhood-onset cerebellar atrophy identifies gain-of-function mutations in the CACNA1G calcium channel gene

Brain ◽  
2018 ◽  
Vol 141 (7) ◽  
pp. 1998-2013 ◽  
Author(s):  
Jean Chemin ◽  
Karine Siquier-Pernet ◽  
Michaël Nicouleau ◽  
Giulia Barcia ◽  
Ali Ahmad ◽  
...  
Keyword(s):  
Calcium Channel ◽  
De Novo ◽  
Mutation Screening ◽  
Cerebellar Atrophy ◽  
De Novo Mutation ◽  
Childhood Onset ◽  
Gain Of Function ◽  
Channel Gene

A PDE10A de novo mutation causes childhood-onset chorea with diurnal fluctuations

2017 ◽  
Vol 32 (11) ◽  
pp. 1646-1647 ◽  
Author(s):  
Silvia Esposito ◽  
Miryam Carecchio ◽  
Davide Tonduti ◽  
Veronica Saletti ◽  
Celeste Panteghini ◽  
...  
Keyword(s):  
De Novo ◽  
De Novo Mutation ◽  
Childhood Onset ◽  
Diurnal Fluctuations
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