This test analyzes GPC3, which is the gene that is most commonly associated with Simpson-Golabi-Behmel syndrome type 1 (SGBS1). This X-linked condition primarily affects males and is characterized by pre- and postnatal overgrowth with organomegaly, distinctive facial features, possible involvement of heart and skeletal system, and an increased risk of embryonal tumors. Carrier females are often asymptomatic, though females may also exhibit features of SGBS1.
Genetic testing of GPC3 may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives. This test is specifically designed for heritable germline mutations and is not appropriate for the detection of somatic mutations in tumor tissue.
Simpson-Golabi-Behmel syndrome type 1 (SGBS1) is a rare overgrowth syndrome that typically presents in the prenatal or neonatal period. Affected males typically have macrosomia and a distinctive facies that may include macrocephaly, coarse facial features, macrostomia, and macroglossia. Other clinical findings may include heart defects, malformed or abnormally large kidneys, an enlarged liver and spleen (hepatosplenomegaly), skeletal abnormalities, and gastrointestinal or genitourinary malformations. Individuals with SGBS1 may have some degree of intellectual disability. SGBS1 is associated with an increased risk for embryonal tumors, including Wilms tumor, hepatoblastoma, adrenal neuroblastoma, gonadoblastoma, and hepatocellular carcinoma.
Although the lifetime risk of developing specific tumors is not well established, individuals with SGBS1 have an increased risk in childhood for developing such tumors as:
Simpson-Golabi-Behmel syndrome type 1 is inherited in an X-linked manner. Females are frequently unaffected carriers, though some may display mild features due to skewed X-inactivation. Approximately 20%–30% of individuals have SGBS1 due to a de novo pathogenic variant.
The prevalence of SGBS1 is currently unknown and appears to be rare.
Analysis of the GPC3 gene may be considered in a personal and/or family history of:
Further details regarding features that are suggestive of SGBS1 can be found: Tenorio J, et al. Simpson-Golabi-Behmel syndrome types I and II. Orphanet J Rare Dis. 2014 Sep 20;9:138.
Clinical diagnostic criteria for SGBS1 have not been established. The diagnosis is based on clinical findings, family history consistent with X-linked inheritance, and molecular genetic testing.
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons and 10 to 20 base pairs of adjacent intronic sequence on either side of the coding exons in the transcript listed below. In addition, the analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any limitations in the analysis of these genes will be listed on the report. Contact client services with any questions.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|