Whole exome sequencing identifies a novel frameshift mutation in GPC3 gene in a patient with overgrowth syndrome

• A novel hemizygous single base pair deletion in exon 8 of GPC3 gene (chrX:132670203delA) results in a frameshift and is likely to create a new stop codon at 62 amino acids downstream to codon 564 (c.1692delT; p.Leu565SerfsTer63) of the protein.
• Instead of causing premature truncation, this frameshift leads to the length of the protein to be increased at the C-terminal end by 46 amino acids
• Diseases with overlapping phenotypes need broad based genetic testing like exome sequencing

Overgrowth syndromes are a heterogeneous group of diseases characterized by focal or generalized overgrowth. Many of the syndromes have overlapping clinical features and it is difficult to diagnose the condition based on clinical features alone. In the present study we report on a patient with overgrowth syndrome where extensive investigation did not reveal the cause of disease. Finally exome sequencing revealed a novel hemizygous single base pair deletion in exon 8 of GPC3 gene (chrX:132670203delA) resulting in a frameshift and creating a new stop codon at 62 amino acids downstream to codon 564 (c.1692delT; p.Leu565SerfsTer63) of the protein. The mutation was confirmed by Sanger sequencing. The mother was found to be heterozygous for the mutation. This variation is not reported in the 1000 Genomes, Exome Variant Server (EVS), Exome Aggregation Consortium (ExAC) and dbSNP databases and the region is conserved across primates. Exome sequencing was helpful in establishing diagnosis of Simpson–Golabi–Behmel syndrome type 1 (SGBS1) in a patient with unknown overgrowth syndrome.