Novel de novo frameshift variant in the ASXL3 gene in a child with microcephaly and global developmental delay
| Autor: | Petra Nikolova, Jan Smetana, Eva Makaturova, Marketa Wayhelova, Jan Oppelt, Renata Gaillyová, Hana Filková, Petr Kuglík, Rastislav Beharka, Eva Hladílková |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Proband Cancer Research Microcephaly medicine.medical_specialty Developmental Disabilities Pilot Projects Central hypotonia Biology Biochemistry Speech Disorders Frameshift mutation 03 medical and health sciences symbols.namesake 0302 clinical medicine Molecular genetics Genetics medicine Humans Global developmental delay Child Frameshift Mutation Molecular Biology Bainbridge-Ropers syndrome Sanger sequencing Articles additional sex-combs like 3 gene medicine.disease Hypotonia Pedigree developmental delay 030104 developmental biology Oncology array-CGH 030220 oncology & carcinogenesis symbols Muscle Hypotonia Molecular Medicine Female next-generation sequencing medicine.symptom Transcription Factors |
| Zdroj: | Molecular Medicine Reports |
| ISSN: | 1791-3004 1791-2997 |
| DOI: | 10.3892/mmr.2019.10303 |
| Popis: | De novo sequence variants, including truncating and splicing variants, in the additional sex-combs like 3 gene (ASXL3) have been described as the cause of Bainbridge-Ropers syndrome (BRS). This pathology is characterized by delayed psychomotor development, severe intellectual disability, growth delay, hypotonia and facial dimorphism. The present study reports a case of a girl (born in 2013) with severe global developmental delay, central hypotonia, microcephaly and poor speech. The proband was examined using a multi-step molecular diagnostics algorithm, including karyotype and array-comparative genomic hybridization analysis, with negative results. Therefore, the proband and her unaffected parents were enrolled for a pilot study using targeted next-generation sequencing technology (NGS) with gene panel ClearSeq Inherited DiseaseXT and subsequent validation by Sanger sequencing. A novel de novo heterozygous frameshift variant in the ASXL3 gene (c.3006delT, p.R1004Efs*21), predicted to result in a premature termination codon, was identified. In conclusion, the present study demonstrated that targeted NGS using a suitable, gene-rich panel may provide a conclusive molecular genetics diagnosis in children with severe global developmental delays. |
| Databáze: | OpenAIRE |
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