Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity.
Sheng-Jia LinBarbara VonaTracy LauKevin HuangMaha S ZakiHuda Shujaa AldeenEhsan Ghayoor KarimianiClarissa RoccaMahmoud M NoureldeenAhmed K SaadCassidy PetreeTobias BartolomaeusRami Abou JamraGiovanni ZifarelliAditi GotkhindikarIngrid M WentzensenMingjuan LiaoEmalyn Elise CorkPratishtha VarshneyNarges HashemiMohammad Hasan MohammadiAboulfazl RadJuanita NeiraMehran Beiraghi ToosiCordula KnoppIngo KurthThomas D ChallmanRebecca SmithAsmahan AbdallaThomas HaafMohnish SuriManali JoshiWendy K ChungAndres Moreno-De-LucaHenry HouldenReza MaroofianGuarav K VarshneyPublished in: Genome medicine (2023)
Based on the results of genetic, clinical, and functional studies, we formed three hypotheses in which to frame observations: biallelic OGDHL variants lead to a highly variable monogenic disorder, variants in OGDHL are following a complex pattern of inheritance, or they may not be causative at all. Our study further highlights the continuing challenges of assessing the validity of reported disease-gene associations and effects of variants identified in these genes. This is particularly more complicated in making genetic diagnoses based on identification of variants in genes presenting a highly heterogenous phenotype such as "OGDHL-related disorders".