Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Medical Affairs, |
RCV001003304 | SCV001161387 | likely pathogenic | Farber lipogranulomatosis | 2019-06-19 | criteria provided, single submitter | literature only | Variant c.593T>C has been assigned a clinical significance of likely pathogenic for the following reasons. Patient (proband) and her sibling presented with Farber disease symptoms characteristic of Type 1 Farber disease described in Gene Reviews (https://www.ncbi.nlm.nih.gov/books/NBK488189/). The patient died at 8 months and her sibling died at 1 year of age. The parent's DNA was sequenced to determine if variants existed in their ASAH1 gene. Two variants, c.997C>G and c.593T>C, were identified in carrier status in the parents indicating biparental segregation of inheritance in the affected daughers. Using minigene functional analysis, the missense mutation, p.V198A, resulted in skipping of exon 8 due to inactivation of an exonic splicing enhancer (ESE) element resulting in a truncated and inactive protein contributing to the severe Farber phenotype in both siblings. |