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A recent case study (PMID:31640787) reported a homozygous variant in FCRL1 that co-segregated with EAST syndrome in a single family comprising four affected individuals. In this study, FCRL1 was one of five candidate genes identified via whole-exome sequencing using variant prioritization pipelines based on autosomal‐recessive inheritance and homozygosity mapping. Although the variant was observed in all four patients, the overall evidence remains limited because no targeted functional assays were performed to directly validate the pathogenicity of FCRL1 in EAST syndrome.
The genetic data suggest that the FCRL1 variant co-segregates with intellectual disability (HP:0001249), a key feature of EAST syndrome (MONDO_0013005), yet the lack of robust experimental and replication data warrants a cautious interpretation for diagnostic decision‑making. Further functional assessments and studies in additional families will be required to strengthen the clinical validity and to elucidate the mechanistic role of FCRL1 in the disease process. This preliminary evidence, however, may serve as a potential marker for further investigations in clinical and research settings.
Gene–Disease AssociationLimitedA homozygous FCRL1 variant was identified in a single family with four affected individuals (PMID:31640787); however, the lack of additional families and direct functional validation constrains the strength of association. Genetic EvidenceLimitedThe variant in FCRL1 segregated in all four affected individuals from one family, meeting minimal genetic criteria but without replication in independent cohorts. Functional EvidenceLimitedNo gene-specific functional assays were reported; functional evidence in the study primarily focused on other genes, leaving the pathogenic mechanism of FCRL1 unconfirmed. |