Molecular analysis of a novel intragenic deletion in GPC3 in three cousins with Simpson-Golabi-Behmel syndrome.
Julia SchmidtRonja HollsteinFrank J KaiserGabriele Gillessen-KaesbachPublished in: American journal of medical genetics. Part A (2017)
Simpson-Golabi-Behmel syndrome (SGBS) is characterized by multiple congenital abnormalities, pre/postnatal overgrowth, distinctive craniofacial features intellectual disability (ID) of variable degree, and an increased risk for embryonal tumors. SGBS is X-linked recessive and caused by deletions, duplications, and point mutations in GPC3, encoding a membrane associated cell surface heparan sulfate proteoglycan named glypican 3. GPC3 plays essential roles in the regulation of cell growth signaling and cell division. Here, we report on a family with three affected cousins who show variable clinical signs of SGBS and ID. Initial microarray-CGH revealed a deletion of approximately 30-50 kb that includes at least one exon of GPC3. By subsequent Sanger sequencing of genomic DNA we could map the chromosomal break points to define a deletion size of 43,617 bp including exons 5 and 6 of the GPC3 gene. RT-PCR analysis on RNA derived from whole blood could further confirm the deletion of both exons on transcript level. This loss of two exons results in a frameshift and a premature stop of translation. Based on our results we have established a breakpoint spanning PCR that could identify the mutation in the mothers and grandmother of the patients. Thus, we provided a molecular test that allows accurate genetic counselling and prenatal diagnosis for this family.
Keyphrases
- intellectual disability
- copy number
- single cell
- autism spectrum disorder
- cell surface
- end stage renal disease
- genome wide
- rna seq
- newly diagnosed
- single molecule
- chronic kidney disease
- prognostic factors
- preterm infants
- case report
- high resolution
- peritoneal dialysis
- stem cells
- cell free
- circulating tumor
- mass spectrometry
- smoking cessation
- transcription factor
- hepatitis c virus
- mesenchymal stem cells
- bone marrow
- high density
- patient reported
- circulating tumor cells
- hiv infected