PT  - JOURNAL ARTICLE
AU  - Iskender, Ceren
AU  - Kartal, Ece
AU  - Akcimen, Fulya
AU  - Kocoglu, Cemile
AU  - Ozoguz, Aslihan
AU  - Kotan, Dilcan
AU  - Eraksoy, Mefkure
AU  - Parman, Yesim G.
AU  - Basak, Ayse Nazli
TI  - Turkish families with juvenile motor neuron disease broaden the phenotypic spectrum of <em>SPG11</em>
AID  - 10.1212/NXG.0000000000000025
DP  - 2015 Oct 01
TA  - Neurology Genetics
PG  - e25
VI  - 1
IP  - 3
4099  - http://ng.neurology.org/content/1/3/e25.short
4100  - http://ng.neurology.org/content/1/3/e25.full
SO  - Neurol Genet2015 Oct 01; 1
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