Methods: Gene panel testing for neuromuscular disorders was performed on Illumina NGS sequencing system and class 4 (likely pathogenic) or 5 (pathogenic) variants were reported and subsequently confirmed by Sanger sequencing.
Results: A de novo heterozygous class 4 variant NM_022068.2(PIEZO2 ): c.8199_8202delAATA p.(Leu2733Phefs*10) in PIEZO2 gene was detected.
Discussion: Congenital arthrogryposis is a broad spectrum of genetic and non-genetic conditions with overlapping clinical features. Heterozygous pathogenic variants in PIEZO2 are known to cause 3 types of arthrogryposis: Gordon syndrome (distal arthrogryposis type 3), Marden-Walker syndrome and Distal arthrogryposis type 5. These clinically and genetically overlapping syndromes are now considered to represent variable expression of the same disorder. Although there is no clear genotype- phenotype correlation, there are some differences among these syndromes. The clinical features of the presented patient tend most to correlate with Gordon syndrome phenotype, which is typically characterized by clenching of hands and feet, camptodactyly, clubfoot, and less frequently, cleft palate. The detected PIEZO2 variant is a frame shift variant, resulting in a premature stop codon. It is located 20 amino acids before the normal stop codon and has not been previously reported. This PIEZO2 gene variant was presumed to be likely pathogenic given that there is another reported patient with proven pathogenic PIEZO2 gene variant that is located downstream of this PIEZO2 position.
Conclusion: A patient with phenotype of Gordon syndrome is presented, one of the three disorders known to be caused by PIEZO2 pathogenic variants.
|Title of host publication||EuroDysmorphology|
|Subtitle of host publication||31th EUROPEAN MEETING ON DYSMORPHOLOGY|
|Number of pages||1|
|Publication status||Published - 21 Sep 2021|
|Event||31th EUROPEAN MEETING ON DYSMORPHOLOGY : Online - Online|
Duration: 23 Sep 2021 → 25 Sep 2021
|Conference||31th EUROPEAN MEETING ON DYSMORPHOLOGY|
|Period||23/09/21 → 25/09/21|