Algorithmic Approach for Methyl-CpG Binding Protein 2 (<i>MECP2</i>) Gene Testing in Patients With Neurodevelopmental Disabilities

Sanmann, Jennifer N.; Schaefer, Gerald; Buehler, Bruce A.; Sanger, Warren G.

doi:10.1177/0883073811424796

Cited by 8 publications

(4 citation statements)

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“…edu.au, last accessed September 26, 2011). Sanmann et al 42 indicated that 48% and 35% of the mutations found in RTT patients were nonsense and missense, respectively. In our group, we found more missense than nonsense mutations, with these two types accounting for 73.3% of all of the mutations found by CSGE or sequencing.…”

Section: Discussionmentioning

confidence: 99%

MECP2 Gene Study in a Large Cohort

Maortua

Martínez-Bouzas

García-Ribes

et al. 2013

The Journal of Molecular Diagnostics

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The MECP2 gene located on Xq28 is one of the most important genes contributing to the spectrum of neurodevelopmental disorders. Therefore, we present our experience in the molecular study of this gene. MECP2 was thoroughly tested for the presence of mutations (sequencing of four exons and rearrangements) in 120 female patients: 28 with classic Rett syndrome, five with atypical Rett syndrome, and 87 with heterogeneous phenotypes with some Rett-like features. Another 120 female patients with intellectual disability of unknown origin were also studied, but in these cases we only tested exons 3 and 4. Finally, 861 healthy controls (519 females and 342 males) were also studied for exon 3 and 4. Eighteen different pathological mutations were found, five of them previously undescribed, and four large deletions detected by multiplex ligation-dependent probe amplification. All were de novo mutations not present in the parents. In conclusion, i) MECP2 is one of the most important genes in the diagnosis of genetic intellectual disability in females; ii) MECP2 must be studied not only in patients with classical/atypical Rett syndrome but also in patients with other phenotypes related to Rett syndrome; and iii) for the new variants, it is important to perform complementary studies, including the analysis of large populations of healthy individuals and the use of in silico programs.

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Section: Discussionmentioning

confidence: 99%

MECP2 Gene Study in a Large Cohort

Maortua

Martínez-Bouzas

García-Ribes

et al. 2013

The Journal of Molecular Diagnostics

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“…RTT, the second most prevalent cause of intellectual disability in the female gender, is characterized by a regression in neurodevelopment between 6 and 18 months of age that severely affects motor, cognitive and communication skills [176,177], with the development of autistic behavior as well [178]. MeCP2, a transcriptional repressor, causes chromatin compaction and gene silence by binding to methylated CG dinucleotides in specific gene promoters [179]. Sometimes it serves as a transcriptional activator [180] and also mediates splicing [181].…”

Section: Rett Syndromementioning

confidence: 99%

Brain Mitochondrial Bioenergetics in Genetic Neurodevelopmental Disorders: Focus on Down, Rett and Fragile X Syndromes

Valenti

Vacca

2023

IJMS

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Mitochondria, far beyond their prominent role as cellular powerhouses, are complex cellular organelles active as central metabolic hubs that are capable of integrating and controlling several signaling pathways essential for neurological processes, including neurogenesis and neuroplasticity. On the other hand, mitochondria are themselves regulated from a series of signaling proteins to achieve the best efficiency in producing energy, in establishing a network and in performing their own de novo synthesis or clearance. Dysfunctions in signaling processes that control mitochondrial biogenesis, dynamics and bioenergetics are increasingly associated with impairment in brain development and involved in a wide variety of neurodevelopmental disorders. Here, we review recent evidence proving the emerging role of mitochondria as master regulators of brain bioenergetics, highlighting their control skills in brain neurodevelopment and cognition. We analyze, from a mechanistic point of view, mitochondrial bioenergetic dysfunction as causally interrelated to the origins of typical genetic intellectual disability-related neurodevelopmental disorders, such as Down, Rett and Fragile X syndromes. Finally, we discuss whether mitochondria can become therapeutic targets to improve brain development and function from a holistic perspective.

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“…Thus, in a medical context, the identification of regression may warrant an evaluation for genetic conditions associated with regression, metabolic disorders, and/or seizure disorders. [13][14][15][16] However, to the best of our knowledge, the frequency with which reported regression prompts a medical workup at time of ASD diagnosis and the developmental profiles of children with ASD and regression prompting medical workup are not yet known.…”

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confidence: 99%

Description of Clinician-Diagnosed Regression at Time of Autism Spectrum Disorder Diagnosis in Toddlers

Zaro

Harris

Sideridis

et al. 2022

J Dev Behav Pediatr

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Objective: Previous studies have reported varying rates of regression in children with autism spectrum disorder (ASD). We sought to (1) determine the rate of clinician-diagnosed regression for young children with ASD and (2) compare developmental functioning and ASD symptoms of children with versus without regression. Methods: We conducted a retrospective chart review of toddlers (age 18-36 months) with Diagnostic and Statistical Manual-5 ASD. We abstracted cognitive, language, adaptive, and motor functioning standard scores and ASD core symptoms. Regression was defined as "clinician-diagnosed regression accompanied by recommendation for a medical workup." We used propensity scores to match each participant with regression (n 5 20) one-to-one with a participant without regression (n 5 20). We compared the groups on developmental scores using independent sample t tests and on core ASD symptoms using Pearson's x 2 test. Results: Of the 500 children with ASD, n 5 20 (4%) had regression (defined above). Children with regression had lower Bayley cognitive and language scores and lower Vineland adaptive scores compared with those without regression (cognitive: 78.0 vs 85.5, p < 0.05; language: 56.9 vs 68.2, p < 0.01; adaptive: 70.0 vs 80.3; p < 0.01). There was no difference in motor scores across groups. There were no significant differences in the frequency of exhibiting core ASD symptoms for those with versus without regression. Conclusion: In this clinical sample of children with ASD, regression was diagnosed in a small percentage (4%). Those with regression had lower cognitive, language, and adaptive skills compared with those without regression. Rates of clinician-diagnosed regression referred for medical workup are significantly lower than prior estimates based on parent report.

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Algorithmic Approach for Methyl-CpG Binding Protein 2 (MECP2) Gene Testing in Patients With Neurodevelopmental Disabilities

Cited by 8 publications

References 122 publications

MECP2 Gene Study in a Large Cohort

MECP2 Gene Study in a Large Cohort

Brain Mitochondrial Bioenergetics in Genetic Neurodevelopmental Disorders: Focus on Down, Rett and Fragile X Syndromes

Description of Clinician-Diagnosed Regression at Time of Autism Spectrum Disorder Diagnosis in Toddlers

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