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. Author manuscript; available in PMC: 2010 Jul 12.
Published in final edited form as: Arch Neurol. 2010 Feb;67(2):161–170. doi: 10.1001/archneurol.2009.328

Table 2. GRN Genetic Variants Observed in This Study.

Coding DNA NM_002087.2 Predicted
Protein
NP_002078.1 		MAF (Count)
 Case Information
 Sourced
Casesa
(n=868)		 Controls 1b
(n=760)		 Controls 2c ID Dx AAO, y FH
Premature Termination Mutations (Pathogenic)
Nonsense mutations
 c.328C>T p.R110X 0.001 (1) NA NA UP74 FTD 52 Possible 21
 c.347C>A p.S116X 0.001 (1) 0.000 (0) NA UP455 FTD 57 Yes Novel
 c.911G>A p.W304X 0.001 (1) NA 0.000 (0/400) UPA118 FTLD-U 73 Yes 11, 21
 c.1009C>T p.Q337X 0.001 (1) NA NA UPA148 FTLD-U 62 Possible 21
 c.1157G>A p.W386X 0.001 (1) NA 0.000 (0/990) UBA1 FTD 59 Yes 9, 11
 c.1252C>T p.R418X 0.001 (1) NA 0.000 (0/400) UPA43e FTLD-U 58 Yes 9, 11, 21
 c.1402C>T p.Q468X 0.001 (1) NA 0.000 (0/590) FPS47 FTD 59 Yes 9
 c.1477C>T p.R493X 0.007 (6) 0.000 (0) 0.000 (0/400) DHH1 CBD 60 Yes 11, 18, 21,
23-26
ORBF2 FTD Unk Yes
VAJ1 FTD 62 Yes
VXM1 FTLD-U 59 Yes
UPA251 FTLD-U 56 Possible
UP403e FTD 45 Yes
Frameshift by indel mutations
 c.90_91insCTGC p.C31LfsX35 0.001 (1) NA 0.000 (0/400) BQL01 FTD Unk Unk 9, 11
 c.299delC p.P100HfsX156 0.001 (1) 0.000 (0) NA LRR1 FTD 60 Yes Novel
 c.388_391del CAGT p.Q130SfsX125 0.001 (1) NA 0.000 (0/400) BKM1 FTD 65 Yes 9, 11
 c.592_593delAG p.R198GfsX19 0.001 (1) 0.000 (0) NA MAQ1 FTD 58 Yes Novel
 c.675_676delCA p.S226WfsX28 0.001 (1) NA 0.000 (0/400) UP525 FTD 56 Possible 11, 21
 c.813_816delCACT p.T272SfsX10 0.001 (1) 0.000 (0) NA UP791 FTD 68 Possible 25, 27
 c.846_852dupGAAATGT p.D285EfsX3 0.001 (1) 0.000 (0) NA LXR1 FTLD-U 53 Yes Novel
 c.1317_1318delCA p.D441HfsX4 0.001 (1) 0.000 (0) NA UP946 CBS 55 Yes Novel
Frameshift by large genomic
 deletion mutation
  c.1414-16_1590del p.A472VfsX10 0.001 (1) 0.000 (0) NA ARC62 CBD 50 No 18
Frameshift by splice site
 mutations
  c.264+2T>C p.V90SfsX67 0.001 (1) 0.000 (0) NA RPN17 FTD 55 Yes 28
  c.348A>C p.A89VfsX139 0.001 (1) 0.000 (0) NA UPA573 FTLD-U 67 Yes Novel
  c.709-2A>G p.A237TfsX6 0.002 (2) 0.000 (0) NA EFe FTLD-U 57 Yes 20, 25, 26, 29
VHAe FTD 65 Yes
  c.1179+2T>C p.V395YfsX29 0.001 (1) 0.000 (0) NA UPA203 FTLD-U 59 Possible Novel
  c.1414-2A>G p.A472VfsX10 0.001 (1) 0.000 (0) NA UP52e FTD 52 Yes Novel
Missense Mutations (Pathogenic)
Altered protein translocation
 c.26C>A p.A9D 0.001 (1) NA 0.000 (0/500) HDDD FTD 62 Yes 11, 30
Altered granulin motif (probable
 pathogenic)
  c.313T>C p.C105R 0.001 (1) 0.000 (0) NA SMF1 FTD 39 Yes 11
Other Coding/Exon Variations (Pathogenic Potential Unknown)
Missense variants (MAF >0.01)
 c.208G>A p.G70S 0.001 (1) 0.001f (1) NA UP192 FTD 55 Possible Novel
 c.229G>A p.V77I 0.001 (1) 0.000 (0) NA EF46 At risk Unk Yes Novel
 c.545C>T p.T182M 0.003 (3) 0.000 (0) 0.000 (0/380) ARC43 MSA 57 Yes 30, 31
NCM1 At risk Unk Yes
FTD12 Pick 58 No
 c.634C>T p.R212W 0.001 (1) 0.001 (1) NA FTD134 FTD Unk Yes Novel
 c.752C>G p.T251S 0.001 (1) 0.000 (0) NA CCW1 FTD 44 Yes Novel
 c.827C>T p.A276V 0.001 (1) 0.000 (0) NA UPA573 Depressiong 50 Unk Novel
 c.893G>A p.R298H 0.001 (1) 0.000 (0) NA UPA147 FTLD-U 70 Unk Novel
 c.970G>A p.A324T 0.001 (1) NA 0.008 (3/367) FPS47 FTD, AD 59 Yes 31
 c.1058G>A p.S353N 0.001 (1) 0.001 (1) NA UPA158 FTLD-U 65 None Novel
 c.1070C>G p.P357R 0.001 (1) 0.000 (0) NA UPA148 FTLD-U 62 Possible Novel
 c.1253G>A p.R418Q 0.002 (2) NA 0.002 (2/1046) FRD17 FTD 83 Unk 11, 30, 32
UPC1793 FTLD/MND Unk No
 c.1297C>T p.R433T 0.006 (5) 0.001 (1) 0.009 (8/930) RPN17 FTD 55 Yes 11, 25, 31, 32
UPA147 FTLD-U 70 Unk
UPA203 FTD 59 Possible
UP528 FTD 61 None
UPC1590 ALS 74 Unk
 c.1544G>C (rs25647) p.G515A 0.001 (1) 0.005f (4) 0.004 (4/1046) GRR1 FTD 57 Yes 11, 31
Silent variants (MAF <0.01)
 c.99C>T p.D33 0.001 (1) NA 0.008 (11/1314) UPC1658 ALS 57 Unk 11, 31, 32
 c.159G>A p.L53 0.001 (1) 0.000 (0) NA UP192 FTD 55 Possible Novel
 c.903G>A p.S301 0.003 (3) 0.000 (0) 0.006 (4/646) HEG1 FALS 60 Yes 11, 32
UPA148 FTLD-U 62 Possible
UP684 FTD 60 Unk
3′UTR variants
 c.*30G>Ah NC 0.001 (1) NA NA UP59 FTD 65 No Novel
 c.*301delTh NC 0.001 (1) NA NA PCK1 Pick Unk No Novel

Abbreviations: AAO, age at onset; AD, Alzheimer disease; ALS, amyotrophic lateral sclerosis; CBD, corticobasal degeneration; CBS, corticobasal syndrome; Dx, diagnosis; FALS, familial ALS; FH, family history; FTD, frontotemporal dementia; FTLD-U, frontotemporal lobar degeneration with ubiquitin-positive inclusions; ID, identifier; indel, insertion-deletions; MAF, minor allele frequency; MND, motor neuron disease; MSA, multiple system atrophy; NA, not available; NC, no change; Unk, unknown; UTR, untranslated region.

a

Frequency in 868 chromosomes of FTD series cases; numbers in parentheses indicate counts.

b

Frequency in our 760 (or 1510) control chromosomes; numbers in parentheses indicate counts.

c

Combined control frequency from the references; numbers in parentheses indicate counts over chromosomes screened.

d

Numbers represent reference numbers.

e

Cases with same mutation also found in additional affected family member.

f

There were 1510 control chromosomes.

g

Diagnosis was originally FTD and later changed to depression.

h

*Stop codon.