title: Novel mutation in forkhead box G1 (FOXG1) gene in an Indian patient with Rett syndrome.
abstract: Rett syndrome (RTT) is a severe neurodevelopmental disorder characterized by the progressive loss of intellectual functioning, fine and gross motor skills and communicative abilities, deceleration of head growth, and the development of stereotypic hand movements, occurring after a period of normal development. The classic form of RTT involves mutation in MECP2 while the involvement of CDKL5 and FOXG1 genes has been identified in atypical RTT phenotype. FOXG1 gene encodes for a fork-head box protein G1, a transcription factor acting primarily as transcriptional repressor through DNA binding in the embryonic telencephalon as well as a number of other neurodevelopmental processes. In this report we have described the molecular analysis of FOXG1 gene in Indian patients with Rett syndrome. FOXG1 gene mutation analysis was done in a cohort of 34 MECP2/CDKL5 mutation negative RTT patients. We have identified a novel mutation (p. D263VfsX190) in FOXG1 gene in a patient with congenital variant of Rett syndrome. This mutation resulted into a frameshift, thereby causing an alteration in the reading frames of the entire coding sequence downstream of the mutation. The start position of the frameshift (Asp263) and amino acid towards the carboxyl terminal end of the protein was found to be well conserved across species using multiple sequence alignment. Since the mutation is located at forkhead binding domain, the resultant mutation disrupts the secondary structure of the protein making it non-functional. This is the first report from India showing mutation in FOXG1 gene in Rett syndrome.
authors.affiliation: Genetic Research Centre, National Institute for Research in Reproductive Health (ICMR), Jahangir Merwanji Street, Parel, Mumbai 400 012, India. Electronic address: dasd@nirrh.res.in.
authors.forename: Dhanjit Kumar
authors.initials: DK
authors.lastname: Das
authors.affiliation: Genetic Research Centre, National Institute for Research in Reproductive Health (ICMR), Jahangir Merwanji Street, Parel, Mumbai 400 012, India.
authors.forename: Vaishali
authors.initials: V
authors.lastname: Jadhav
authors.affiliation: Genetic Research Centre, National Institute for Research in Reproductive Health (ICMR), Jahangir Merwanji Street, Parel, Mumbai 400 012, India.
authors.forename: Vikas C
authors.initials: VC
authors.lastname: Ghattargi
authors.affiliation: Department of Pediatric Neurology, Hinduja National Hospital and Research Centre, Mahim, Mumbai 400 016, India.
authors.forename: Vrajesh
authors.initials: V
authors.lastname: Udani
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002648:Child; D005260:Female; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000235:genetics*; D016368:Frameshift Mutation; D006801:Humans; D007194:India; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D015518:Rett Syndrome / Q000175:diagnosis / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: C090173:FOXG1 protein, human; D051858:Forkhead Transcription Factors; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D009419:Nerve Tissue Proteins; D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human
keywords: DNA sequencing; FOXG1; MECP2; Mutation; Rett syndrome