Molecular analysis of a novel intragenic deletion in GPC3 in three cousins with Simpson–Golabi–Behmel syndrome

Julia Schmidt*, Ronja Hollstein, Frank J. Kaiser, Gabriele Gillessen-Kaesbach

*Corresponding author for this work
2 Citations (Scopus)


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.

Original languageEnglish
JournalAmerican Journal of Medical Genetics, Part A
Issue number5
Pages (from-to)1400-1405
Number of pages6
Publication statusPublished - 05.2017


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