The association between FBN1 and Shprintzen-Goldberg Syndrome was first reported in 1996 by Sood et al. (PMID: 8563763). However, the FBN1 variant in this report has been found at a higher than expected frequency in the general population and is therefore not considered evidence in this evaluation. Two additional missense variants described in PMIDs: 19293843 and 27160103 have been observed at frequencies in the general population too high to be considered as evidence. Three additional variants described in PMIDs: 8563763, 16333834, and 19293843 were not evaluated as the clinical presentation of the affected individuals was more consistent with Marfan syndrome than Shprintzen-Goldberg Syndrome. In 2012, heterozygous pathogenic variants in the gene SKI were reported as the genetic cause of Shprintzen-Goldberg Syndrome (PMIDs: 23023332, 23103230). In summary, the evidence supporting an association between Shprintzen-Goldberg Syndrome and FBN1 is disputed. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on 12/01/2021.
The relationship between FBN1 and Shprintzen-Goldberg syndrome was first reported in 1996 by Sood et al. (PMID: 8563763). However, the FBN1 variant in this report has been found at a higher than expected frequency in the general population and is therefore not considered evidence in this evaluation. Two additional missense variants (PMIDs: 19293843, 27160103) have been observed at frequencies in the general population too high to be considered as evidence. Three additional variants (PMIDs: 8563763, 16333834, 19293843) were not evaluated as the clinical presentation of the affected individuals was more consistent with Marfan syndrome than Shprintzen-Goldberg syndrome. In 2012, heterozygous pathogenic variants in the gene SKI were reported as the genetic cause of Shprintzen-Goldberg syndrome (PMIDs: 23023332, 23103230).
In summary, the evidence supporting a relationship between Shprintzen-Goldberg syndrome and FBN1 is disputed. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on December 1, 2021 (SOP Version 9).
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