RT Journal Article SR Electronic T1 Turkish families with juvenile motor neuron disease broaden the phenotypic spectrum of SPG11 JF Neurology Genetics JO Neurol Genet FD Lippincott Williams & Wilkins SP e25 DO 10.1212/NXG.0000000000000025 VO 1 IS 3 A1 Iskender, Ceren A1 Kartal, Ece A1 Akcimen, Fulya A1 Kocoglu, Cemile A1 Ozoguz, Aslihan A1 Kotan, Dilcan A1 Eraksoy, Mefkure A1 Parman, Yesim G. A1 Basak, Ayse Nazli YR 2015 UL http://ng.neurology.org/content/1/3/e25.abstract AB Objective: Identification of causative mutations in 3 consanguineous families (with 4 affected members) referred to our center with young-onset motor neuron disease and overlapping phenotypes resembling autosomal recessive juvenile amyotrophic lateral sclerosis (ARJALS) and autosomal recessive hereditary spastic paraplegia (ARHSP).Methods: Patients have a slowly progressive motor neuron disease with upper and lower motor neuron dysfunction. There is distal muscle weakness and atrophy associated with pyramidal signs. Whole-exome sequencing was performed on the patients and the unaffected parent samples to identify disease-causing mutations. Variants were prioritized according to their predicted pathogenicity and their relevance to the clinical phenotypes.Results: Five distinct homozygous mutations within the SPG11 gene were identified, 3 of which were novel and truncating: c.7155T>G/p.Tyr2385Ter, c.2250delT/p.Phe750Leufs*3, and c.1966_1967delAA/p.Lys656Valfs*11. The copresence of 2 distinct homozygous missense variations was observed in 2 families: c.6224A>G/p.Asn2075Ser and c.7132T>C/p.Phe2378Leu. The segregation of these variations in the family members was validated by Sanger sequencing.Conclusions: Four patients with juvenile-onset motor neuron disease with consanguineous parents were found to carry homozygous mutations in the SPG11 gene. Our findings confirm the overlapping phenotypes of SPG11-based ARJALS and ARHSP, indicating that these 2 entities may be the extreme phenotypes of the same disease continuum with many common features. This, in turn, confirms the difficult differential diagnosis of these 2 diseases in the clinic.ALS=amyotrophic lateral sclerosis; ARHSP=autosomal recessive hereditary spastic paraplegia; ARJALS=autosomal recessive juvenile amyotrophic lateral sclerosis; HSP=hereditary spastic paraplegia; LMN=lower motor neuron; TCC=thin corpus callosum; UMN=upper motor neuron; WES=whole-exome sequencing