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A homozygous missense variant in the PLCB4 gene causes severe phenotype of auriculocondylar syndrome type 2 |
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| Authors: | Khawla El Fizazi Abdelhamid Bouramtane Meriame Abbassi Yasser Ali El Asri Omar Askander Mustapha El Fahime Karim Ouldim Mohammed Ridal Laila Bouguenouch |
| Institution: | 1. Faculty of Medicine, Pharmacy and Dentistry, Laboratory of Biomedical and Translational Research, Sidi Mohamed Ben Abdellah University, Fez, Morocco;2. Unit of Medical Genetics and Oncogenetics, Hassan II University Hospital, Fez, Morocco;3. Superior Institute of Biological and Paramedical Sciences, Faculty of Medical Sciences, Mohamed VI Polytechnic University, Benguerir, Morocco;4. National Center for Scientific and Technological Research, Rabat, Morocco;5. Faculty of Medicine, Pharmacy and Dentistry, Laboratory of Biomedical and Translational Research, Sidi Mohamed Ben Abdellah University, Fez, Morocco
Unit of Medical Genetics and Oncogenetics, Hassan II University Hospital, Fez, Morocco;6. Department of Otorhinolaryngology, Hassan II University Hospital, Fez, Morocco Faculty of Medicine, Pharmacy and Dentistry, Laboratory of Anatomy, Microsurgery and Experimental Surgery, Sidi Mohamed Ben Abdellah University, Fez, Morocco |
| Abstract: | Auriculocondylar syndrome (ARCND) is a rare craniofacial birth defect characterized by malformations in the mandible and external ear (Question Mark Ear). Genetically, three distinct subtypes of ARCND (ARCND1, ARCND2, and ARCND3) have been identified. ARCND2 is linked to pathogenic variants in the PLCB4 gene (phospholipase C β4). PLCB4 is a key effector of the EDN1-EDNRA pathway involved in craniofacial development via the induction, migration, and maintenance of neural crest cells. ARCND2 is typically inherited in an autosomal dominant pattern, with recessive inheritance pattern being rare. In this study, we report the first homozygous missense variant (NM_000933.4: c.2050G>A: p.(Gly684Arg)) in the PLCB4 gene causing ARCND in a 3-year-old patient with a severe clinical phenotype of the syndrome. The patient presented with typical craniofacial ARCND features, in addition to intestinal transit defect, macropenis, and hearing loss. These findings further delineate the phenotypic spectrum of ARCND associated with autosomal recessive PLCB4 loss of function variants. Notably, our results provide further evidence that these variants can result in a more severe and diverse manifestations of the syndrome. Clinicians should consider the rare features of this condition for better management of patients. |
| Keywords: | auriculocondylar syndrome exome sequencing PLCB4 question mark ear |