Combined MECP2 duplication syndrome and ADNP syndrome in a Chinese boy: a case report and literature review DOI Creative Commons

Yun-Xiu Fan,

Yang Wu,

Hongwen Zhang

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: July 31, 2023

Abstract Background Methyl-CpG-binding protein 2 (MECP2) acts as a transcriptional repressor or activator regulating the genes associated with nerve system development. The increased copy number of MECP2 can cause new X‑linked intellectual disability syndrome named duplication (MDS), which is characterized by broad range neurodevelopmental abnormalities, well hypotonia, recurrent respiratory infections, and facial dysmorphism. ADNP caused heterozygous de novo mutations in Activity Dependent Neuroprotective Protein (ADNP) gene, global developmental delay, disability, language impairment, autism spectrum, variable extraneurologic features. We reported here first infant case combined MDS syndrome. Case presentation A 6-month boy was hospitalized complaint cough fever for 7 days. He born at 40 weeks gestation intrauterine growth retardation. had pneumonia twice since birth, 1-month 4-month, respectively. showed obviously weight height retardation birth. His motor milestone delayed. Physical examination revealed no abnormal dysmorphic Except other ophthalmologic deficits were observed. Genetic analysis that carried chromosome g.151283637_154348425dup, this area contains Xq28 region (includes MECP2). also variant heterozygously, c.2194_2197del (p.Leu732MetfsTer20), exon 5. fulfilled diagnostic criteria Conclusion identified X g.151283637_154348425dup (p.Leu732MetfsTer20) clinical features hypotonia China.

Language: Английский

NAP (Davunetide): The Neuroprotective ADNP Drug Candidate Penetrates Cell Nuclei Explaining Pleiotropic Mechanisms DOI Creative Commons

Maram Ganaiem,

Nina D. Gildor,

Shula Shazman

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(18), P. 2251 - 2251

Published: Sept. 11, 2023

(1) Background: Recently, we showed aberrant nuclear/cytoplasmic boundaries/activity-dependent neuroprotective protein (ADNP) distribution in ADNP-mutated cells. This malformation was corrected upon neuronal differentiation by the ADNP-derived fragment drug candidate NAP (davunetide). Here, investigated mechanism of nuclear protection. (2) Methods: CRISPR/Cas9 DNA-editing established N1E-115 neuroblastoma cell lines that express two different green fluorescent proteins (GFPs)-labeled mutated ADNP variants (p.Tyr718* and p.Ser403*). Cells were exposed to conjugated Cy5, followed live imaging. further characterized using quantitative morphology/immunocytochemistry/RNA quantifications. (3) Results: rapidly distributed cytoplasm also seen nucleus. Furthermore, reduced microtubule content observed lines. In parallel, disrupting microtubules zinc or nocodazole intoxication mimicked mutation phenotypes resulted nuclear-cytoplasmic boundaries, which treatment. No effects noted on levels. Ketamine, used as a control, ineffective, but both ketamine exhibited direct interactions with ADNP, via silico docking. (4) Conclusions: Through microtubule-linked mechanism, localized cytoplasmic compartments, ameliorating ADNP-related deficiencies. These novel findings explain previously published gene expression results broaden (davunetide) utilization research clinical development.

Language: Английский

Citations

11
Helsmoortel-Van Der Aa Syndrome (HVDAS) DOI

Ali Alishvandi,

Sara Hanaei

Published: Jan. 1, 2025

Citations

0
From synaptic dysfunction to atypical emotional processing in autism DOI Open Access
Sara L. Reis, Patrícia Monteiro

FEBS Letters, Journal Year: 2024, Volume and Issue: 598(3), P. 269 - 282

Published: Jan. 17, 2024

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition mainly characterized by social impairments and repetitive behaviors. Among these core symptoms, notable aspect of ASD the presence emotional complexities, including high rates anxiety disorders. The inherent heterogeneity poses unique challenge in understanding its etiological origins, yet utilization diverse animal models replicating traits has enabled researchers to dissect intricate relationship between autism atypical processing. In this review, we delve into general findings about neural circuits underpinning one most extensively researched evolutionarily conserved states: fear anxiety. Additionally, explore how distinct exhibit various phenotypes, making them crucial tool for dissecting ASD's multifaceted nature. Overall, proper display response, it properly process integrate sensorial visceral cues fear‐induced stimuli. individuals altered sensory processing, possibly contributing emergence phobias, prevailing manifested population. Moreover, distinctive alterations pivotal processing hub, amygdala. By examining neurobiological mechanisms underlying regulation, can gain insights factors profile observed with ASD. Such hold potential pave way more targeted interventions therapies that address challenges faced within spectrum.

Language: Английский

Citations

1
Patient with Helsmoortel-van der Aa Syndrome and O’Donnell-Luria-Rodan Syndrome: a case report DOI Creative Commons
Ana Beatriz Deleame Medeiros, D. Coutinho,

Rafael Patricio dos Santos Alarcón

et al.

Brazilian Journal of Case Reports, Journal Year: 2023, Volume and Issue: 4(2), P. 9 - 16

Published: July 31, 2023

Heterozygous pathogenic variants in the ADNP gene cause Helsmoortel-van der Aa syndrome which is an autosomal dominant mutation, whose patients have autism spectrum disorder (ASD) and intellectual disability. Pathogenic KTM2E are related to O’Donnell-Luria-Rodan syndrome, also dominant, characterized by global development delay. The case of a male patient, only child, born at term measuring 45 cm (z-1) weighing 2.460 kg (z-2) was described. patient presented short stature, disorder, delay neuropsychomotor development, gastrointestinal reflux, hyperopia, recurrent infections, constipation. result from whole exome sequencing (WES) identified two uncertain significance (VUS) KMT2E genes, literature compatible signs symptoms with those found patient.

Language: Английский

Citations

0
Combined MECP2 duplication syndrome and ADNP syndrome in a Chinese boy: a case report and literature review DOI Creative Commons

Yun-Xiu Fan,

Yang Wu,

Hongwen Zhang

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: July 31, 2023

Abstract Background Methyl-CpG-binding protein 2 (MECP2) acts as a transcriptional repressor or activator regulating the genes associated with nerve system development. The increased copy number of MECP2 can cause new X‑linked intellectual disability syndrome named duplication (MDS), which is characterized by broad range neurodevelopmental abnormalities, well hypotonia, recurrent respiratory infections, and facial dysmorphism. ADNP caused heterozygous de novo mutations in Activity Dependent Neuroprotective Protein (ADNP) gene, global developmental delay, disability, language impairment, autism spectrum, variable extraneurologic features. We reported here first infant case combined MDS syndrome. Case presentation A 6-month boy was hospitalized complaint cough fever for 7 days. He born at 40 weeks gestation intrauterine growth retardation. had pneumonia twice since birth, 1-month 4-month, respectively. showed obviously weight height retardation birth. His motor milestone delayed. Physical examination revealed no abnormal dysmorphic Except other ophthalmologic deficits were observed. Genetic analysis that carried chromosome g.151283637_154348425dup, this area contains Xq28 region (includes MECP2). also variant heterozygously, c.2194_2197del (p.Leu732MetfsTer20), exon 5. fulfilled diagnostic criteria Conclusion identified X g.151283637_154348425dup (p.Leu732MetfsTer20) clinical features hypotonia China.

Language: Английский

Citations

0