TY - JOUR
T1 - Phenotypic Diversity in GNAO1 Patients
T2 - A Comprehensive Overview of Variants and Phenotypes
AU - Sáez González, Maria
AU - Kloosterhuis, Kes
AU - van de Pol, Laura
AU - Baas, Frank
AU - Mikkers, Harald
N1 - Publisher Copyright: © 2023 Maria Sáez González et al.
PY - 2023
Y1 - 2023
N2 - GNAO1 disorder is a rare autosomal dominant neurodevelopmental syndrome that is clinically manifested by developmental delay, (early onset) epilepsy, and movement disorders. Clinical symptoms appear very heterogeneous in nature and severity, as well as the response of GNAO1 patients to available medication varies. Pathogenic GNAO1 variants have been found mainly scattered throughout the gene although certain mutation hotspots affecting the function of the encoded Gαo proteins exist. GNAO1 variants only partially explain the diverse phenotypic spectrum observed but full stratification has been hampered by the limited number of patients. The aim of this review was to generate a comprehensive overview of the germline variants in GNAO1 and provide insight into the phenotypic diversity of the GNAO1 disorder. We compiled a list of 398 GNAO1 germline variants. In addition, we provide the GNAO1 variants and associated phenotypes of 282 GNAO1 patients reported in case reports, whole genome sequencing studies, genetic variant databases, and 8 novel GNAO1 patients that were not described before. This has resulted in a list of 107 (likely) pathogenic GNAO1 variants. Available phenotypic data was utilized to quantitatively assess the genetic and phenotypic diversity of the GNAO1 disorder and discuss the outcomes. This inventory forms the basis for a GNAO1 variant database that will be updated continuously. Moreover, it will aid genetic diagnostics, medical decision-making, prognostication, and research on the mechanisms underlying the GNAO1 disorder.
AB - GNAO1 disorder is a rare autosomal dominant neurodevelopmental syndrome that is clinically manifested by developmental delay, (early onset) epilepsy, and movement disorders. Clinical symptoms appear very heterogeneous in nature and severity, as well as the response of GNAO1 patients to available medication varies. Pathogenic GNAO1 variants have been found mainly scattered throughout the gene although certain mutation hotspots affecting the function of the encoded Gαo proteins exist. GNAO1 variants only partially explain the diverse phenotypic spectrum observed but full stratification has been hampered by the limited number of patients. The aim of this review was to generate a comprehensive overview of the germline variants in GNAO1 and provide insight into the phenotypic diversity of the GNAO1 disorder. We compiled a list of 398 GNAO1 germline variants. In addition, we provide the GNAO1 variants and associated phenotypes of 282 GNAO1 patients reported in case reports, whole genome sequencing studies, genetic variant databases, and 8 novel GNAO1 patients that were not described before. This has resulted in a list of 107 (likely) pathogenic GNAO1 variants. Available phenotypic data was utilized to quantitatively assess the genetic and phenotypic diversity of the GNAO1 disorder and discuss the outcomes. This inventory forms the basis for a GNAO1 variant database that will be updated continuously. Moreover, it will aid genetic diagnostics, medical decision-making, prognostication, and research on the mechanisms underlying the GNAO1 disorder.
UR - http://www.scopus.com/inward/record.url?scp=85176142658&partnerID=8YFLogxK
U2 - https://doi.org/10.1155/2023/6628283
DO - https://doi.org/10.1155/2023/6628283
M3 - Review article
SN - 1059-7794
VL - 2023
JO - Human mutation
JF - Human mutation
M1 - 6628283
ER -