Further phenotypic delineation of the auriculocondylar syndrome type 2 with literature review.
Ewelina M OlechAnna Sowinska-SeidlerFilip ŁojekDelfina PopielJoanna Walczak-SztulpaAleksander JamsheerPublished in: Journal of applied genetics (2020)
Auriculocondylar syndrome (ACS) is an ultra-rare disorder that arises from developmental defects of the first and second pharyngeal arches. Three subtypes of ACS have been described so far, i.e., ACS1 (MIM: 602483), ACS2 (MIM: 600810), and ACS3 (MIM: 131240). The majority of patients, however, are affected by ACS2, which results from the mutations in the PLCB4 gene. Herein, we have described an 8-year-old male patient presenting with ACS2 and summarized the molecular and phenotypic spectrum of the syndrome. We have also compared the clinical features of our case to three other previously described cases (one sporadic and two familial) harboring the same heterozygous missense variant c.1862G>A, p.Arg621His in the PLCB4 gene. The mutation was detected using whole-exome sequencing (WES). Due to low coverage of WES and suspicion of somatic mosaicism, the variant was additionally reassessed by deep targeted next-generation sequencing panel of genes related to the craniofacial disorders, and next confirmed by Sanger sequencing. ACS2 presents high intra- and interfamilial phenotypic heterogeneity that impedes reaching an exact clinical and molecular diagnosis. Thus, describing additional cases, carrying even the known mutation, but resulting in variable phenotypes, is essential for better understanding of such orphan Mendelian diseases.
Keyphrases
- acute coronary syndrome
- case report
- copy number
- genome wide
- newly diagnosed
- end stage renal disease
- single cell
- ejection fraction
- genome wide identification
- early onset
- transcription factor
- dna methylation
- intellectual disability
- single molecule
- autism spectrum disorder
- molecular dynamics
- mass spectrometry
- cell free
- circulating tumor
- drug induced