Familial frontotemporal dementia with neuronal intranuclear inclusions is not a polyglutamine expansion disease

Mackenzie, Ian R; Butland, Stefanie L; Devon, Rebecca S; Dwosh, Emily; Feldman, Howard; Lindholm, Caroline; Neal, Scott J; Ouellette, BF Francis; Leavitt, Blair R

doi:10.1186/1471-2377-6-32

BMC Neurology

Table 1 Genetic analysis of FTLD-U DNA samples reveals no significant CAG/CAA repeat expansions in candidate polyglutamine-encoding genes.

From: Familial frontotemporal dementia with neuronal intranuclear inclusions is not a polyglutamine expansion disease

	Gene Name (associated polyQ disease, CAA/CAG tract length of smallest disease-cuasing allele) ^a	Control Samples (n = 94) estimated CAA/CAG tract length	FTD Patients estimated CAA/CAG tract length
			case 1^b	case 2^b	case 3^b	case 4^b	case 5^b	case 6^c
A	AR (SBMA, 38)	10–37	22	19	20	21, 23	19	24
	ATN1 (DRPLA, 48)	10–39	18, 23	18, 20	20, 23	19	15, 19	15
	ATXN1 (SCA1, 39)	6–39	15, 20	15, 20	16	15, 20	15, 20	14, 21
	ATXN2 (SCA2, 37)	25–41	22	22	22	22	22	22
	ATXN3 (SCA3/MJD, 51)	14–42	15	9	9	9	17	na
	ATXN7 (SCA7, 36)	4–35	10	11	10	10	10	10
	CACNA1A (SCA6, 20)	4–18	12, 21 ^d	13, 16	15	14	14	13
	HD (HD, 36)	10–35	14, 15	12, 17	17, 21	15, 17	12, 14	12
	TBP (SCA17, 49)	38–61	39, 44	38, 41	38, 43	36, 39	38, 47	38, 42
B	ARID3B	11–13	12	12	12, 16	12, 16	13, 16	13
	ASCL1	5–24	13, 17	13	13, 17	13, 18	13, 18	12
	BMP2K	22–31	26	26	26	26	26	26
	C14orf4	19–24	22, 25	22, 25	23	23	24	23
	CXorf6	11–12	12	12	12	11	11	12
	DCP1B	10–12	12	na	12	11, 12	11, 12	11, 12
	KCNN3	10–43	18	17, 18	na	19, 21	18, 21	18, 20
	MED12	26	27	26	26	26	26	26
	MEF2A	9–16	12, 15	11	12	10, 11	11, 14	11
	MINK1	5–6	6	6	6	6	6	7
	MLL2	6–9	9	9	9	9	9	9
	NCOA3	25–34	26, 29	28	26, 28	29	28, 29	28
	NCOA6	23–26	25	25	na	24	25	25
	NCOR2	13–22	17, 19	17	17	16, 17	13, 17	17, 18
	NFAT5	18–21	19	18	18	18	na	na
	NM 014856	13–17	16	17	14, 16	17	16	14, 16
	NUMBL	26	18, 20	18	20	18, 20	18, 20	20
	PCQAPa	10–18	11	11	11	10	10	11
	PCQAPb	11–22	17	16	16	15	16	16
	PHLDA1	15–19	15	15	16	15	15	15
	POLG	13–16	13	14	13	16, 17	13	13
	POU3F2	20–21	15	21, 22	21	21	21	21
	POU6F2	7–11	10	10	10	10	10	10
	PRDM10	7–8	8	8	8	8	8	8
	PRKCBP1	7–11	8	8	7	8	8	8
	RAI1	8–20	14	14	14	14	14	10, 14
	RUNX2	26–53	22	21	22	23	23	21
	SATB1	12–21	15	15	15	15	15	15
	SMARCA2	18–25	22	22	22	22	22	22
	SOCS7	7–22	8, 12	8	8	8	8	8
	TFEB	9–15	12	9	9	9	10	10
	TNRC4	14–17	15	15	15	15	15	15
	TNRC6B	7–10	9, 10	9	9	9	8	8
	TNS	8–11	10, 12	10	9	10	9	10
	ZNF161	8–22	16, 17	14, 20	14	na	14	14
	ZNF384	11–20	15	16	15	15	20	15
C	ARID1B	16–23	18	18	19	19	18	18
	BAIAP1	16–21	20, 24	19, 25	18, 19	19	20	17, 19
	BRD4	8–9	8	8	8	8	8	8
	C9orf43	8–9	9	9, 12	8	8	9, 12	8
	CHERP	12	12	12	12	12	12	12
	CIZ1	6	6	6	6	6	6	6
	CREBBP	18	18	18	18	18	18	18
	EP400	28–31	30	30, 34	30	30	31	30, 34
	FOXP2	34–40	41	na	41	41	42	42
	KIAA1817	26–27	27	28	28	28	27	27
	KIAA2018	11–16	13	14	14	14	12, 17	12
	MAML2	27–31	29	32, 36	28	28	28, 31	28
	MAML3b	18	19	19	19	19	19	19
	MN1	26–30	28	28	28	28	28	28, 29
	PAXIP1L	7	9	9	9	8	8	8
	PHC1	13–15	15	15	15	15	15	15
	ST6GALNAC5	12–14	12	12	12	12	12	12
	THAP11	18–30	24	24	24, 33	24	24, 26	24, 28
	TNRC6A	4–8	4, 8	5, 8	8	8	5, 8	8

^a Genes identified in a computational analysis of polyglutamine repeat-containing genes in the human genome. A) Genes known to cause disease via polyglutamine expansion. B) Patient and control samples were both assessed by high resolution agarose gel electrophoresis. C) Control samples were analyzed by capillary electrophoresis (Butland et al., in submission) and patient samples analyzed by high resolution agarose gel electrophoresis.
^b FTDL-U patients with NII.
^c FTDL-U patient without NII.
^d Alleles 6 or more b.p. longer than the largest contol allele (putative expanded alleles) appear in bold type.
Samples of FTLD-U patient DNA with NII (Cases 1–5) and without NII (Case 6) were screened for expansions in the CAG/CAA trinucleotide repeat tracts of our candidate genes including known disease genes (A). The CAG/CAA repeat lengths from the FTLD-U subjects were compared with published normal values and with those of healthy controls (n = 94), assessed by high resolution agarose gel electrophoresis (B), and/or capillary electrophoresis (C). For the few alleles estimated to be equal to or slightly larger than the maximum measured in our control samples (bold), the CAG/CAA repeat length was confirmed by capillary electrophoresis on an ABI 3700 sequencer using GeneMapper software. Using this approach, no clinically significant CAG/CAA repeat expansions were identified in the DNA from any of our FTLD-U patients.

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ISSN: 1471-2377

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