Details

Autor(en) / Beteiligte

• Vineeth, Venugopal S.
• Dutta, Usha R.
• Tallapaka, Karthik
• Das Bhowmik, Aneek
• Dalal, Ashwin

Titel

Whole exome sequencing identifies a novel 5 Mb deletion at 14q12 region in a patient with global developmental delay, microcephaly and seizures

Ist Teil von

• Gene, 2018-10, Vol.673, p.56-60

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2018

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Rett syndrome is a neurodevelopmental disorder affecting the nervous, musculoskeletal and gastroenteric systems. Affected individuals show normal neonatal development for 6–18 months followed by sudden growth arrest, psychomotor retardation and a broad spectrum of clinical features. Sequence variants in MECP2 gene have been identified as the major genetic etiology accounting for 90–95% of patients. Apart from MECP2, pathogenic sequence variants and copy number variants of FOXG1 gene lead to congenital type of Rett syndrome which is a more severe form and characterised by absence of early normal development as seen in classical Rett syndrome. In this report we describe a female child with global developmental delay, microcephaly and myoclonic seizures harbouring a 5 Mb deletion in 14q12 locus resulting in deletion of single copy of brain specific genes FOXG1, PRKD1 and NOVA1. Whole exome sequencing ruled out any possible role of other pathogenic single nucleotide variants and/or indels as the etiology for the observed phenotype. However, copy number variation analysis from the whole exome data detected a ~ 5 Mb microdeletion at the long arm of chromosome 14q12 region. The deletion was confirmed through array Comparative Genomic Hybridization and validated by quantitative PCR. Further, parents were analysed for mosaicism through metaphase Fluorescence in-situ Hybridisation. Our report broadens the phenotype of atypical Rett syndrome and reiterates the role of exome sequencing not only in detection of point mutation/small indels but also for detection of large deletions/duplication in coding regions. •A novel ~5Mb microdeletion at 14q12 is identified by exome sequencing in a patient with severe intellectual disability.•The deleted region encompasses three important genes (NOVA1, FOXG1, PRKD1) with brain specific expression and function.•Microdeletion involving FOXG1 gene on 14q12 region confirm the diagnosis as congenital type Rett syndrome.•The report shows the utility of exome sequencing not only for detecting SNVs but also CNVs in the coding regions.