TY - JOUR T1 - Heterozygous <em>KIF1A</em> variants underlie a wide spectrum of neurodevelopmental and neurodegenerative disorders JF - Journal of Medical Genetics JO - J Med Genet DO - 10.1136/jmedgenet-2020-107007 SP - jmedgenet-2020-107007 AU - Francesco Nicita AU - Monia Ginevrino AU - Lorena Travaglini AU - Stefano D'Arrigo AU - Giovanna Zorzi AU - Renato Borgatti AU - Gaetano Terrone AU - Michela Catteruccia AU - Gessica Vasco AU - Vesna Brankovic AU - Sabrina Siliquini AU - Silvia Romano AU - Chiara Veredice AU - Marina Pedemonte AU - Michelina Armando AU - Donatella Lettori AU - Fabrizia Stregapede AU - Luca Bosco AU - Antonella Sferra AU - Valeria Tessarollo AU - Romina Romaniello AU - Giovanni Ristori AU - Enrico Bertini AU - Enza Maria Valente AU - Ginevra Zanni Y1 - 2020/07/31 UR - http://jmg.bmj.com/content/early/2020/07/31/jmedgenet-2020-107007.abstract N2 - Background Dominant and recessive variants in the KIF1A gene on chromosome 2q37.3 are associated with several phenotypes, although only three syndromes are currently listed in the OMIM classification: hereditary sensory and autonomic neuropathy type 2 and spastic paraplegia type 30, both recessively inherited, and mental retardation type 9 with dominant inheritance.Methods In this retrospective multicentre study, we describe the clinical, neuroradiological and genetic features of 19 Caucasian patients (aged 3–65 years) harbouring heterozygous KIF1A variants, and extensively review the available literature to improve current classification of KIF1A-related disorders.Results Patients were divided into two groups. Group 1 comprised patients with a complex phenotype with prominent pyramidal signs, variably associated in all but one case with additional features (ie, epilepsy, ataxia, peripheral neuropathy, optic nerve atrophy); conversely, patients in group 2 presented an early onset or congenital ataxic phenotype. Fourteen different heterozygous missense variants were detected by next-generation sequencing screening, including three novel variants, most falling within the kinesin motor domain.Conclusion The present study further enlarges the clinical and mutational spectrum of KIF1A-related disorders by describing a large series of patients with dominantly inherited KIF1A pathogenic variants ranging from pure to complex forms of hereditary spastic paraparesis/paraplegias (HSP) and ataxic phenotypes in a lower proportion of cases. A comprehensive review of the literature indicates that KIF1A screening should be implemented in HSP regardless of its mode of inheritance or presentations as well as in other complex neurodegenerative or neurodevelopmental disorders showing congenital or early onset ataxia. ER -