Familial GPC3 and GPC4-TFDP3 deletions at Xq26 associated with Simpson-Golabi-Behmel syndrome

We report a familial case of Simpson-Golabi-Behmel syndrome type 1 (SGBS1) with prenatal ultrasound findings of bilateral ventriculomegaly and polyhydramnios and postnatal findings of macroglossia, macrosomia and other dysmorphic features. Oligonucleotide array comparative genomic hybridization (aCGH) analysis and further polymerase chain reaction (PCR) sequencing identified a 167.071 kb hemizygous deletion including the entire TFDP3 gene and exons 3-9 of the GPC4 (Glypican 4) gene, and a 86.943 kb deletion including exon 3 of the GPC3 (Glypican 3) gene. Joined sequences at the breakpoints indicate that the deletion of TFDP3 and GPC4 is likely caused by microhomology-mediated end joining while the deletion within the GPC3 gene is due to non-homology end joining. Both deletions are considered loss of function due to the loss of large portions of coding sequences. The prenatal ultrasound findings of the affected male fetuses in this family are comparable with two previously reported cases with large deletions of the GPC3 and GPC4 genes. Further investigation of more cases with genetic defects of both GPC3 and GPC4 genes is needed for assessing the genotype-phenotype correlation.