Objective: To (1) describe the genetic variability, phenotype and epidemiology of spastin mutation in HSPpatients (2) create the UK HSP register with a focus on patients with mutations in the SPAST gene. Background: Hereditary Spastic Paraplegias (HSP) are a heterogeneous group of rare degenerative diseasesthat present clinically with a very diverse phenotype. Spastin (SPAST) mutations are the most common causeof HSP and have been classifi ed initially as predominantly “pure” form. Several complex spastin phenotypeshave been published recently. Methods: We analysed, retrospectively, genetic, phenotype and investigations results data from 117genetically confi rmed spastin cases from 98 families from UK population. For each mutation we assessednovelty, pathogenicity and genotype-phenotype correlation. Results: A total of 74 unique mutations were identifi ed of which 37.8% (28) were novel. 80% of mutationswere unique to one kindred only. All types of variants were identifi ed with missense mutations being themost frequent (39%). Males were more frequently affected with M:F ratio 1.7:1. Mean age at onset was29.5y with a range from birth to 63y. Over 30% of cases had an early onset HSP. Complex phenotype waspresent in 18.6%. Our results show an unexpectedly high rate (9.8%) of spastin cases associated withpsychiatric illnesses of which three cases had autistic spectrum disorders. One mutation, thec.1635_1636insAA was identifi ed in four cases from three unrelated families affected by Asperger, severedepression and schizoaffective disorder. This is a novel Frameshift mutation with a frequency of 3.3% in ourcohort. All the mutations associated with psychiatric manifestations are loss of function, produce a truncatedprotein and are located in the AAA domain.We found that a later onset and a complex phenotype produced amore severe disease and a faster rate of progression. No other genotype-phenotype correlation was possibleand a high variability was identifi ed between and within families. Conclusions: This study, one of the largest collections of genetically confi rmed spastin patients to date,provides new insights into SPAST related HSP. In particular, the previously under-recognized associationwith autism and psychiatric illness needs to be confi rmed in other genes and cohorts to determine if this is aspecifi c effect of spastin mutations. To cite this abstract in AMA style: V. Chelban, A. Tucci, H. Houlden. Development of the UK hereditary spastic paraplegia registry: Analysisof SPAST patients reveals high rate of psychiatric comorbidities [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/development-of-the-uk-hereditary-spastic-paraplegia-registry-analysis-of-spast-patients-reveals-high-rate-of-psychiatric-comorbidities/. AccessedDecember 4, 2023. MDS Abstracts - https://www.mdsabstracts.org/abstract/development-of-the-uk-hereditary-spastic-paraplegia-registry-analysis-of-spast-patients-reveals-high-rate-of-psychiatric-comorbidities/