TY - JOUR
T1 - Case report :
T2 - Identification of a novel variant p.Gly215Arg in the CHN1 gene causing Moebius syndrome
AU - Manso-Bazús, Carmen
AU - Spataro, Nino
AU - Gabau, Elisabeth
AU - Beltrán-Salazar, Viviana P.
AU - Trujillo-Quintero, Juan Pablo
AU - Capdevila, Núria
AU - Brunet Vega, Anna
AU - Baena Díez, Neus
AU - Jeyaprakash, A Arockia
AU - Martinez-Glez, Víctor
AU - Ruiz, Anna
N1 - Copyright © 2024 Manso-Bazús, Spataro, Gabau, Beltrán-Salazar, Trujillo-Quintero, Capdevila, Brunet-Vega, Baena, Jeyaprakash, Martinez-Glez and Ruiz.
PY - 2024/1/31
Y1 - 2024/1/31
N2 - Background: Moebius Syndrome (MBS) is a rare congenital neurological disorder characterized by paralysis of facial nerves, impairment of ocular abduction and other variable abnormalities. MBS has been attributed to both environmental and genetic factors as potential causes. Until now only two genes, PLXND1 and REV3L have been identified to cause MBS. Results: We present a 9-year-old male clinically diagnosed with MBS, presenting facial palsy, altered ocular mobility, microglossia, dental anomalies and congenital torticollis. Radiologically, he lacks both abducens nerves and shows altered symmetry of both facial and vestibulocochlear nerves. Whole-exome sequence identified a de novo missense variant c.643G>A; p.Gly215Arg in CHN1, encoding the alpha 2-chimaerin protein. The p.Gly215Arg variant is located in the C1 domain of CHN1 where other pathogenic gain of function variants have been reported. Bioinformatic analysis and molecular structural modelling predict a deleterious effect of the missense variant on the protein function. Conclusion: Our findings support that pathogenic variants in the CHN1 gene may be responsible for different cranial congenital dysinnervation syndromes, including Moebius and Duane retraction syndromes. We propose to include CHN1 in the genetic diagnoses of MBS.
AB - Background: Moebius Syndrome (MBS) is a rare congenital neurological disorder characterized by paralysis of facial nerves, impairment of ocular abduction and other variable abnormalities. MBS has been attributed to both environmental and genetic factors as potential causes. Until now only two genes, PLXND1 and REV3L have been identified to cause MBS. Results: We present a 9-year-old male clinically diagnosed with MBS, presenting facial palsy, altered ocular mobility, microglossia, dental anomalies and congenital torticollis. Radiologically, he lacks both abducens nerves and shows altered symmetry of both facial and vestibulocochlear nerves. Whole-exome sequence identified a de novo missense variant c.643G>A; p.Gly215Arg in CHN1, encoding the alpha 2-chimaerin protein. The p.Gly215Arg variant is located in the C1 domain of CHN1 where other pathogenic gain of function variants have been reported. Bioinformatic analysis and molecular structural modelling predict a deleterious effect of the missense variant on the protein function. Conclusion: Our findings support that pathogenic variants in the CHN1 gene may be responsible for different cranial congenital dysinnervation syndromes, including Moebius and Duane retraction syndromes. We propose to include CHN1 in the genetic diagnoses of MBS.
KW - Chn1
KW - Congenital dysinnervation syndromes
KW - Genetic diagnosis
KW - Moebius syndrome
KW - Novel variant
UR - http://www.scopus.com/inward/record.url?scp=85185269937&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/3a150227-f312-371b-9679-d982974915e0/
U2 - 10.3389/fgene.2024.1291063
DO - 10.3389/fgene.2024.1291063
M3 - Article
C2 - 38356699
SN - 1664-8021
VL - 15
JO - Frontiers in Genetics
JF - Frontiers in Genetics
M1 - 1291063
ER -