Biallelic Variants in the Ectonucleotidase ENTPD1 Cause a Complex Neurodevelopmental Disorder with Intellectual Disability, Distinct White Matter Abnormalities, and Spastic Paraplegia.
Daniel G CalameIsabella HermanReza MaroofianAren E MarshallKarina Carvalho DonisJawid M FatihTadahiro MitaniHaowei DuChristopher M GrochowskiSergio B SousaCharul GijavanekarSomayeh BakhtiariYoko A ItoClarissa RoccaJill V HunterVernon Reid SuttonLisa T EmrickKym M BoycottAlexander LossosYakov FelligEugenia PrusYosef KalishVardiella MeinerManon SuerinkClaudia RuivenkampKayla MuirheadNebal W SaadiMaha S ZakiArjan BoumanTahsin Stefan BarakatDavid L SkidmoreMatthew OsmondThiago Oliveira SilvaDavid MurphyEhsan Ghayoor KarimianiYalda JamshidiAsaad Ghanim JaddoaHoma TajsharghiSheng Chih JinMohammad Reza AbbaszadeganReza Ebrahimzadeh-VesalSusan HosseiniShahryar AlaviAmir BahreiniElahe ZareanMohammad Mehdi SalehiNouriya Abbas Al-SannaaGiovanni ZifarelliPeter BauerSimon C RobsonZeynep Coban-AkdemirLorena TravagliniFrancesco NicitaShalini N JhangianiRichard A GibbsJennifer E PoseyMichael C KruerKristin D KernohanJonas A Morales SauteHenry HouldenAdeline VanderverSarah H ElseaDavut PehlivanDana MarafiJames R. LupskiPublished in: Annals of neurology (2022)
The ENTPD1 locus trait consists of childhood disease onset, ID, progressive spastic paraparesis, dysarthria, dysmorphisms, and white matter abnormalities, with some individuals showing neurocognitive regression. Investigation of an allelic series of ENTPD1 (1) expands previously described features of ENTPD1-related neurological disease, (2) highlights the importance of genotype-driven deep phenotyping, (3) documents the need for global collaborative efforts to characterize rare autosomal recessive disease traits, and (4) provides insights into disease trait neurobiology. ANN NEUROL 2022;92:304-321.