Screening for novel hexanucleotide repeat expansions at ALS- and FTD-associated loci.
OBJECTIVE
To determine whether GGGGCC (G4C2) repeat expansions at loci other than C9orf72 serve as common causes of amyotrophic lateral sclerosis (ALS).


METHODS
We assessed G4C2 repeat number in 28 genes near known ALS and frontotemporal dementia (FTD) loci by repeat-primed PCR coupled with fluorescent fragment analysis in 199 patients with ALS (17 familial, 182 sporadic) and 136 healthy controls. We also obtained blood from patients with ALS4 for evaluation of repeats surrounding the SETX gene locus. C9orf72 expansions were evaluated in parallel.


RESULTS
Expansions of G4C2 repeats in C9orf72 explained 8.8% of sporadic and 47% of familial ALS cases analyzed. Repeat variance was observed at one other locus, RGS14, but no large expansions were observed, and repeat sizes were not different between cases and controls. No G4C2 repeat expansions were identified at other ALS or FTD risk loci or in ALS4 cases.


CONCLUSIONS
G4C2 expansions near known ALS and FTD loci other than C9orf72 are not a common cause of ALS.
Department of Neurology (F.H., C.F.-R., B.C.C., E.L.F., S.A.G., P.K.T.) and Department of Human Genetics (J.M.J., M.H.M.), University of Michigan, Ann Arbor; Veteran Association Health System (B.C.C., P.K.T.), Ann Arbor; and National Center for Biotechnology Information (D.Z.), National Institutes of Health, Bethesda, MD.
Fang
F
He
Department of Neurology (F.H., C.F.-R., B.C.C., E.L.F., S.A.G., P.K.T.) and Department of Human Genetics (J.M.J., M.H.M.), University of Michigan, Ann Arbor; Veteran Association Health System (B.C.C., P.K.T.), Ann Arbor; and National Center for Biotechnology Information (D.Z.), National Institutes of Health, Bethesda, MD.
Julie M
JM
Jones
Department of Neurology (F.H., C.F.-R., B.C.C., E.L.F., S.A.G., P.K.T.) and Department of Human Genetics (J.M.J., M.H.M.), University of Michigan, Ann Arbor; Veteran Association Health System (B.C.C., P.K.T.), Ann Arbor; and National Center for Biotechnology Information (D.Z.), National Institutes of Health, Bethesda, MD.
Claudia
C
Figueroa-Romero
Department of Neurology (F.H., C.F.-R., B.C.C., E.L.F., S.A.G., P.K.T.) and Department of Human Genetics (J.M.J., M.H.M.), University of Michigan, Ann Arbor; Veteran Association Health System (B.C.C., P.K.T.), Ann Arbor; and National Center for Biotechnology Information (D.Z.), National Institutes of Health, Bethesda, MD.
Dapeng
D
Zhang
Department of Neurology (F.H., C.F.-R., B.C.C., E.L.F., S.A.G., P.K.T.) and Department of Human Genetics (J.M.J., M.H.M.), University of Michigan, Ann Arbor; Veteran Association Health System (B.C.C., P.K.T.), Ann Arbor; and National Center for Biotechnology Information (D.Z.), National Institutes of Health, Bethesda, MD.
Eva L
EL
Feldman
Department of Neurology (F.H., C.F.-R., B.C.C., E.L.F., S.A.G., P.K.T.) and Department of Human Genetics (J.M.J., M.H.M.), University of Michigan, Ann Arbor; Veteran Association Health System (B.C.C., P.K.T.), Ann Arbor; and National Center for Biotechnology Information (D.Z.), National Institutes of Health, Bethesda, MD.
Stephen A
SA
Goutman
Department of Neurology (F.H., C.F.-R., B.C.C., E.L.F., S.A.G., P.K.T.) and Department of Human Genetics (J.M.J., M.H.M.), University of Michigan, Ann Arbor; Veteran Association Health System (B.C.C., P.K.T.), Ann Arbor; and National Center for Biotechnology Information (D.Z.), National Institutes of Health, Bethesda, MD.
Miriam H
MH
Meisler
Department of Neurology (F.H., C.F.-R., B.C.C., E.L.F., S.A.G., P.K.T.) and Department of Human Genetics (J.M.J., M.H.M.), University of Michigan, Ann Arbor; Veteran Association Health System (B.C.C., P.K.T.), Ann Arbor; and National Center for Biotechnology Information (D.Z.), National Institutes of Health, Bethesda, MD.
Brian C
BC
Callaghan
Department of Neurology (F.H., C.F.-R., B.C.C., E.L.F., S.A.G., P.K.T.) and Department of Human Genetics (J.M.J., M.H.M.), University of Michigan, Ann Arbor; Veteran Association Health System (B.C.C., P.K.T.), Ann Arbor; and National Center for Biotechnology Information (D.Z.), National Institutes of Health, Bethesda, MD.
Peter K
PK
Todd