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An early seizure variant type of a male Rett syndrome patient with a MECP2 p.Arg133His missense mutation.

ABSTRACT: BACKGROUND:The clinical spectrum of Rett syndrome (RTT; Mendelian Inheritance in Man [MIM] #312750) in males is considered to be wider than previously expected. Therefore, the existence of RTT with a normal male karyotype is still controversial. Here, we report the first case of a male patient presenting with an early seizure type of Rett-like phenotypes with a missense variant of MECP2. METHOD:An 8-month-old male was admitted to the pediatric department due to an initial seizure event following aspiration pneumonia and was referred to our clinic for the evaluation of unexplained neuroregression. Genomic DNA was prepared from venous blood by standard procedures and was processed at the Yale Center for Genome Analysis (YCGA) for whole exome sequencing (WES). Processing of sequence data, variant calling, and the identification of de novo mutations were then performed. Direct Sanger sequencing was performed following PCR amplification. RESULT:In this patient with a normal karyotype, WES analysis led to the identification of a novel, de novo missense variant of MECP2 (p.Arg133His) that is not observed in the normal population. CONCLUSION:This rare case of an p.Arg133His hemizygous MECP2 missense mutation could guide future treatment and follow-up plans for RETT-like phenotypes.

SUBMITTER: Yoon JA

PROVIDER: S-EPMC6418348 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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An early seizure variant type of a male Rett syndrome patient with a MECP2 p.Arg133His missense mutation.

Yoon Jin A JA Yoo Yongjin Y Lee Je Sang JS Kim Young Mi YM Shin Yong Beom YB

Molecular genetics & genomic medicine 20181219 3

<h4>Background</h4>The clinical spectrum of Rett syndrome (RTT; Mendelian Inheritance in Man [MIM] #312750) in males is considered to be wider than previously expected. Therefore, the existence of RTT with a normal male karyotype is still controversial. Here, we report the first case of a male patient presenting with an early seizure type of Rett-like phenotypes with a missense variant of MECP2.<h4>Method</h4>An 8-month-old male was admitted to the pediatric department due to an initial seizure ...[more]

PMID: 30569584

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Project description:Rett syndrome (RTT) is a rare neurodevelopmental disorder characterized by severe cognitive, social, and physical impairments resulting from de novo mutations in the X-chromosomal methyl-CpG binding protein gene 2 (MECP2). While there is still no cure for RTT, exploring up-to date neurofunctional diagnostic markers, discovering new potential therapeutic targets, and searching for novel drug efficacy evaluation indicators are fundamental. Multiple neuroimaging studies on brain structure and function have been carried out in RTT-linked gene mutation carriers to unravel disease-specific imaging features and explore genotype-phenotype associations. Here, we reviewed the neuroimaging literature on this disorder. MRI morphologic studies have shown global atrophy of gray matter (GM) and white matter (WM) and regional variations in brain maturation. Diffusion tensor imaging (DTI) studies have demonstrated reduced fractional anisotropy (FA) in left peripheral WM areas, left major WM tracts, and cingulum bilaterally, and WM microstructural/network topology changes have been further found to be correlated with behavioral abnormalities in RTT. Cerebral blood perfusion imaging studies using single-photon emission CT (SPECT) or PET have evidenced a decreased global cerebral blood flow (CBF), particularly in prefrontal and temporoparietal areas, while magnetic resonance spectroscopy (MRS) and PET studies have contributed to unraveling metabolic alterations in patients with RTT. The results obtained from the available reports confirm that multimodal neuroimaging can provide new insights into a complex interplay between genes, neurotransmitter pathway abnormalities, disease-related behaviors, and clinical severity. However, common limitations related to the available studies include small sample sizes and hypothesis-based and region-specific approaches. We, therefore, conclude that this field is still in its early development phase and that multimodal/multisequence studies with improved post-processing technologies as well as combined PET-MRI approaches are urgently needed to further explore RTT brain alterations.

Dataset Information

An early seizure variant type of a male Rett syndrome patient with a MECP2 p.Arg133His missense mutation.

Publications

An early seizure variant type of a male Rett syndrome patient with a MECP2 p.Arg133His missense mutation.

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