학술논문
A homozygous missense variant in the PLCB4 gene causes severe phenotype of auriculocondylar syndrome type 2.
Document Type
Academic Journal
Author
El Fizazi K; 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.; Bouramtane A; Unit of Medical Genetics and Oncogenetics, Hassan II University Hospital, Fez, Morocco.; Abbassi M; Unit of Medical Genetics and Oncogenetics, Hassan II University Hospital, Fez, Morocco.; El Asri YA; Unit of Medical Genetics and Oncogenetics, Hassan II University Hospital, Fez, Morocco.; Askander O; Superior Institute of Biological and Paramedical Sciences, Faculty of Medical Sciences, Mohamed VI Polytechnic University, Benguerir, Morocco.; El Fahime M; National Center for Scientific and Technological Research, Rabat, Morocco.; Ouldim K; 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.; Ridal M; 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.; Bouguenouch L; 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.
Source
Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 101235741 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1552-4833 (Electronic) Linking ISSN: 15524825 NLM ISO Abbreviation: Am J Med Genet A Subsets: MEDLINE
Subject
Language
English
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.
(© 2023 Wiley Periodicals LLC.)
(© 2023 Wiley Periodicals LLC.)