title: Turkish families with juvenile motor neuron disease broaden the phenotypic spectrum of SPG11.
abstract: 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.
authors.affiliation: Department of Molecular Biology and Genetics (C.I., E.K., F.A., C.K., A.O., A.N.B.), Neurodegeneration Research Laboratory (NDAL), Suna and Inan Kirac Foundation, Bogazici University, Istanbul, Turkey; Department of Neurology (D.K.), Faculty of Medicine, Sakarya University, Turkey; and Department of Neurology (M.E., Y.P.), Istanbul Medical School, Istanbul University, Turkey.
authors.forename: Ceren
authors.initials: C
authors.lastname: Iskender
authors.affiliation: Department of Molecular Biology and Genetics (C.I., E.K., F.A., C.K., A.O., A.N.B.), Neurodegeneration Research Laboratory (NDAL), Suna and Inan Kirac Foundation, Bogazici University, Istanbul, Turkey; Department of Neurology (D.K.), Faculty of Medicine, Sakarya University, Turkey; and Department of Neurology (M.E., Y.P.), Istanbul Medical School, Istanbul University, Turkey.
authors.forename: Ece
authors.initials: E
authors.lastname: Kartal
authors.affiliation: Department of Molecular Biology and Genetics (C.I., E.K., F.A., C.K., A.O., A.N.B.), Neurodegeneration Research Laboratory (NDAL), Suna and Inan Kirac Foundation, Bogazici University, Istanbul, Turkey; Department of Neurology (D.K.), Faculty of Medicine, Sakarya University, Turkey; and Department of Neurology (M.E., Y.P.), Istanbul Medical School, Istanbul University, Turkey.
authors.forename: Fulya
authors.initials: F
authors.lastname: Akcimen
authors.affiliation: Department of Molecular Biology and Genetics (C.I., E.K., F.A., C.K., A.O., A.N.B.), Neurodegeneration Research Laboratory (NDAL), Suna and Inan Kirac Foundation, Bogazici University, Istanbul, Turkey; Department of Neurology (D.K.), Faculty of Medicine, Sakarya University, Turkey; and Department of Neurology (M.E., Y.P.), Istanbul Medical School, Istanbul University, Turkey.
authors.forename: Cemile
authors.initials: C
authors.lastname: Kocoglu
authors.affiliation: Department of Molecular Biology and Genetics (C.I., E.K., F.A., C.K., A.O., A.N.B.), Neurodegeneration Research Laboratory (NDAL), Suna and Inan Kirac Foundation, Bogazici University, Istanbul, Turkey; Department of Neurology (D.K.), Faculty of Medicine, Sakarya University, Turkey; and Department of Neurology (M.E., Y.P.), Istanbul Medical School, Istanbul University, Turkey.
authors.forename: Aslihan
authors.initials: A
authors.lastname: Ozoguz
authors.affiliation: Department of Molecular Biology and Genetics (C.I., E.K., F.A., C.K., A.O., A.N.B.), Neurodegeneration Research Laboratory (NDAL), Suna and Inan Kirac Foundation, Bogazici University, Istanbul, Turkey; Department of Neurology (D.K.), Faculty of Medicine, Sakarya University, Turkey; and Department of Neurology (M.E., Y.P.), Istanbul Medical School, Istanbul University, Turkey.
authors.forename: Dilcan
authors.initials: D
authors.lastname: Kotan
authors.affiliation: Department of Molecular Biology and Genetics (C.I., E.K., F.A., C.K., A.O., A.N.B.), Neurodegeneration Research Laboratory (NDAL), Suna and Inan Kirac Foundation, Bogazici University, Istanbul, Turkey; Department of Neurology (D.K.), Faculty of Medicine, Sakarya University, Turkey; and Department of Neurology (M.E., Y.P.), Istanbul Medical School, Istanbul University, Turkey.
authors.forename: Mefkure
authors.initials: M
authors.lastname: Eraksoy
authors.affiliation: Department of Molecular Biology and Genetics (C.I., E.K., F.A., C.K., A.O., A.N.B.), Neurodegeneration Research Laboratory (NDAL), Suna and Inan Kirac Foundation, Bogazici University, Istanbul, Turkey; Department of Neurology (D.K.), Faculty of Medicine, Sakarya University, Turkey; and Department of Neurology (M.E., Y.P.), Istanbul Medical School, Istanbul University, Turkey.
authors.forename: Yesim G
authors.initials: YG
authors.lastname: Parman
authors.affiliation: Department of Molecular Biology and Genetics (C.I., E.K., F.A., C.K., A.O., A.N.B.), Neurodegeneration Research Laboratory (NDAL), Suna and Inan Kirac Foundation, Bogazici University, Istanbul, Turkey; Department of Neurology (D.K.), Faculty of Medicine, Sakarya University, Turkey; and Department of Neurology (M.E., Y.P.), Istanbul Medical School, Istanbul University, Turkey.
authors.forename: Ayse Nazli
authors.initials: AN
authors.lastname: Basak