Scrutinizing the molecular, biochemical, and cytogenetic attributes in subjects with Rett syndrome (RTT) and their mothers

• Published in: Epilepsy & behavior 2020-10, Vol.111, p.107277-107277, Article 107277
• Main Authors: Meyyazhagan, Arun, Balasubramanian, Balamuralikrishnan, Kathannan, Sankar, Alagamuthu, Karthick Kumar, Easwaran, Murugesh, Shanmugam, Sureshkumar, Pappusamy, Manikantan, Bhotla, Haripriya Kuchi, Mustaqahamed, Shafiahammedkhan, Arumugam, Vijaya Anand, Kaul, Tanushri, Keshavarao, Sasikala
• Format: Article
• Language: English
• Subjects: Adolescent; Biochemical; Child; Child, Preschool; Cytogenetic abnormalities; Cytogenetic Analysis - methods; Female; Humans; In Situ Hybridization, Fluorescence - methods; MeCP2; Methyl-CpG-Binding Protein 2 - genetics; Molecular Diagnostic Techniques - methods; Mothers; Mutation - genetics; Rett syndrome; Rett Syndrome - diagnosis; Rett Syndrome - genetics; Serotonin; XCI; Young Adult
• ISSN: 1525-5050; 1525-5069
• DOI: 10.1016/j.yebeh.2020.107277

Rett syndrome (RTT) is a stern dominant progressive neurological development disorder linked with X chromosome ranking second for mental slowdown, exclusively in females after few months of birth with normal development and growth period. Genetically any defects in universally expressed methyl-CpG binding protein 2 (MeCP2) transcription regulator gene are considered as radix for RTT in almost all the previous studies. Our study mainly focuses in unraveling the genetic alterations like identifying MeCP2 gene polymorphisms, chromosomal abnormalities, or X-chromosome inactivation (XCI) as underlying cause of RTT in prototypes sorted through Diagnostic and Statistical Manual of Mental Disorders-Text Revised (DSM IV). In addition, we have examined the probable surrogates of brain function disabilities like serotonin, homocysteine (Hcy), calcium, potassium, and lead from blood in both RTT porotypes and their mothers. In our investigation, we have observed varied amino acid substitution of MeCP2 and varied frequency of skewed XCI in RTT prototype. Our study validates that the demonstration of chromosomal analysis, biochemical analysis, and genomic observations helps in concluding RTT condition and can be helpful in providing appropriate treatment and counseling as well as improve the currently available protocol of diagnosis. [Display omitted] •Rett syndrome(RTT)-Progressive neurodevelopment disorder, X-linked mental retardation, foremost in females, defect in MeCP2.•Amino acid substitution-MeCP2 of the RTT-with C to T transition-exon 2 of MeCP2-results in R106W amino acid substitution.•95% confidence interval as degree of skewing in XCI in RTT subjects than mothers.•Novel mutation of MECP2 gene can help in futuristic therapeutic modulation.