SGBS1 = Simpson-Golabi-Behmel syndrome type 1

See Table A. Genes and Databases for chromosome locus and protein.

See Molecular Genetics for information on variants detected in this gene.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include missense, nonsense, and splice site variants and small intragenic deletions/insertions; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications. Exome and genome sequencing may be able to detect deletions/duplications using breakpoint detection or read depth; however, sensitivity can be lower than gene-targeted deletion/duplication analysis.

Chromosomal microarray analysis (CMA) uses oligonucleotide or SNP arrays to detect genome-wide large deletions/duplications (including GPC3 and GPC4) that cannot be detected by sequence analysis. The ability to determine the size of the deletion/duplication depends on the type of microarray used and the density of probes in the Xq26.2 regions.

Data derived from the subscription-based professional view of Human Gene Mutation Database [Stenson et al 2020] and Klein et al, unpublished data. Of note, most reported individuals are males. Molecular causes reported in females to date include heterozygous GPC3 and GPC4 duplication (3 individuals), GPC3 deletion (2 individuals), balanced X-chromosome translocations (2 individuals), and a heterozygous GPC3 duplication (1 individual).

Vuillaume et al [2018]

Contiguous deletions of GPC3 and GPC4 have been identified in multiple families with SGBS1 [Veugelers et al 1998, Schirwani et al 2019, Peng et al 2023]. There are case reports of multigene deletions that extend into GPC4, and a single case of SGBS1 with a pathogenic variant in GPC4; however, the role of GPC4 in SGBS1 pathogenesis remains unknown [Waterson et al 2010]. Intragenic pathogenic GPC4 variants have not been described in isolation and are usually an extension of a deletion that includes GPC3 [Spencer et al 2016]. Duplication of exons 1-9 in GPC4 without deletion or mutation of GPC3 was found in the original family described by Golabi & Rosen [1984] in which no GPC3 pathogenic variant had been identified [Waterson et al 2010]. DiMaio et al [2017] reported a familial case of SGBS1 caused by deletion of GPC3, TFDP3, and GPC4. Schirwani et al [2019] identified one family that had a pathogenic deletion extending into both GPC3 and GPC4. Sha et al [2022] described another unique multigene deletion encompassing GPC3, GPC4, and other genes in a fetus with features of SGBS1.