Table 1.

All known patients with either mutations in or deletions of TGIF

Patienta	HPE typeb	Inheritance	DNA alteration	Predicted protein alteration	Predicted functional alterationc	Gender	Proband (or relationship to proband)	Reference
1a	mic	pat	c.83C>G	p. Ser28Cys	decreased transcriptional repression	F	proband	Gripp et al., 2000
1b	mic	pat	c.83C>G	p. Ser28Cys	decreased transcriptional repression	M	father	Gripp et al., 2000
1c	mic	U	c.83C>G	p. Ser28Cys	decreased transcriptional repression	M	paternal grandfather	Gripp et al., 2000
2a	U	pat	c.91G>C	p. Ala31Pro	U	F	proband	this report
2b	none	U	c.91G>C	p. Ala31Pro	U	M	father	this report
3a	L	mat	c.132G>T	p. Lys44Asn	U	M	proband	Richieri-Costa and Ribeiro, 2008
3b	none	U	c.132G>T	p. Lys44Asn	U	F	mother	Richieri-Costa and Ribeiro, 2008
4	L	de novo	c.133G>T	p. Glu45X	protein truncation with no transcriptional repression	M	proband	El-Jaick et al., 2007
5	U	U	c.228C>A	p. His76Gln	likely no functional alteration	U	proband	El-Jaick et al., 2007
6a	S	pat/mat	c.l40_141delTG (pat); c.228C>A (mat)	p. Ser46fs (pat); p. His76Gln (mat)	paternal mutation results in truncation and loss of repression; maternal mutation likely causes no functional alteration	F	proband	El-Jaick et al., 2007
6b	none	U	c.228C>A	p. His76Gln	likely no functional alteration	F	mother	El-Jaick et al., 2007
6c	none	U	c.140 141delTG	p. Ser46fs	protein truncation with no transcriptional repression	M	father	El-Jaick et al., 2007
7a	S	pat	c.177C>G	p. Tyr59X	protein truncation with no transcriptional repression	F	proband	Aguilella et al., 2003
7b	mic	U	c.177C>G	p. Tyr59X	protein truncation with no transcriptional repression	M	father	Aguilella et al., 2003
8	L	de novo	c.187C>G	p. Pro63Arg	likely misfolded with no transcriptional repression	U	proband	Gripp et al., 2000
9a	A	mat	c.257delT	p. Phe86Serfs*13	likely protein truncation	F	proband	this report
9b	none	U	c.257delT	p. Phe86Serfs*13	likely protein truncation	F	mother	this report
10	A	de novo	c.268C>T	p. Arg90Cys	U	M	proband	Chen et al, 2002
11a	S	pat	c.271C>T	p. Arg91Cys	U	F	proband	this report
11b	A	pat	not available; likely same as 11a	not available; likely same as 11a	U	F	sibling	this report
11c	none	U	c.271C>T	p. Arg91Cys	U	M	father	this report
12a	U	mat	not available; likely same as 12b	not available; likely same as 12b	likely no functional alteration	F	proband	Aguilella et al, 2003
12b	U	U	c.320A>T	p. Glnl07Leu	likely no functional alteration	F	mother	Aguilella et al, 2003; El-Jaick et al, 2007
13a	L	mat	c.377T>C	p. Vall26Ala	U	M	proband	Chen etal, 2006
13b	S	mat	not available; likely same as 13a	not available; likely same as 13a	U	U	sibling	Chen etal, 2006
13c	L	mat	not available; likely same as 13a	not available; likely same as 13a	U	U	sibling	Chen etal, 2006
13d	mic	U	c.377T>C	p. Vall26Ala	U	F	mother	Chen etal, 2006
14	U	U	c.436G>T	p. Alal46Ser	U	M	proband	this report
15	S	U	c.451A>GinrGiF; (SHH: c.l283_1291del)	p. Thrl51ArainTGIF, (SHH: p.378_380del)	likely no functional alteration	F	proband	Nannietal, 1999; Gripp et al, 2000
16a	mic	pat	c.485C>T	p. Serl62Phe	likely no functional alteration	M	proband	Gripp et al, 2000; El-Jaick et al, 2007
16b	none	U	c.485C>T	p. Serl62Phe	likely no functional alteration	M	father	Gripp et al, 2000
17a	U	pat	c.778delC	p. Arg260Glyfs*58	likely misfolded with absent TGF-β-dependent transcriptional repression and decreased RXR-dependent transcriptional repression	M	proband	El-Jaick et al, 2007
17b	mic	U	c.778delC	p. Arg260Glyfs*58	likely misfolded with TGF-β and decreased RXR-dependent transcriptional repression	M	father	El-Jaick et al, 2007
18	L	U	c.778delC	p. Arg260Glyfs*58	likely misfolded with TGF-β and decreased RXR-dependent transcriptional repression	F	proband	this report (no evidence of relationship with family 17, and the 2 families are of different ethnicities)
19	A	U	gene deletion (FISH)	N/A	predicted null	M	proband	Bendavid et al., 2006
20	S	U	gene deletion (MLPA)	N/A	predicted null	U	proband	Bendavid et al., 2009
21	S	mat (both SHH mutation and 18p deletion)	del(18)(pll.23→pter) (SHH: C.1270OG)	N/A in TGIF; (SHH: p. Pro424Ala)	predicted null in TGIF	F	proband	Nannietal., 1999
22a	mic	mat	del(18)(pll.3→18pter)	N/A	predicted null	M	proband	Portnoi et al., 2007
22b	mic	U	del(18)(pll.3→18pter)	N/A	predicted null	F	mother	Portnoi et al., 2007
23	U	U	del(18)(pll.l→18pter)	N/A	predicted null	F	proband	Kuchle et al., 1991
24	mic	de novo	del(18)(pll→18pter)	N/A	predicted null	F	proband	Morales-Peralta and Lanti-gua, 1994
25	U	U	del(18)(pll→18pter)	N/A	predicted null	M	proband	Boudailliez et al., 1983
26	U	de novo	del(18)(p)(l/2ofl8p)	N/A	predicted null	F	proband	Faust et al., 1976
27	L	U	del(18)(p)(3/4ofl8p)	N/A	predicted null	F	proband	Faust et al., 1976
28	mic	de novo	del(18)(p)	N/A	predicted null	F	proband	Aughton et al., 1991
29	mic	de novo	del(18)(p)	N/A	predicted null	M	proband	Dolanetal., 1981
30	L	U	arr(18): 140,284-14,065,199	N/A	predicted null	F	proband	Rosenfeld et al., 2010
31	mic	U	arr(18): chr 18: 5,982-14,065,199	N/A	predicted null	F	proband	Rosenfeld et al., 2010
32	mic	de novo	arr(18): chr 18: 5,982-14,065,199	N/A	predicted null	F	proband	Rosenfeld et al., 2010
33	mic	U	arr(18): 102,328-15,079,388	N/A	predicted null	M	proband	Rosenfeld et al., 2010
34	U	de novo	arr(18): 140,284-10,600,909	N/A	predicted null	F	proband	Rosenfeld et al., 2010
35	mic	U	arr(18): 5,982-4,974,551	N/A	predicted null	F	proband	Rosenfeld et al., 2010
36	A	de novo	arr(18): 5,982-4,974,551	N/A	predicted null	F	proband	Sepulveda, 2009
37	mic	U	del(18)(p11.2→pter)	N/A	predicted null	M	proband	this report
38	mic	U	gene deletion (aCGH)	N/A	predicted null	M	proband	this report

Some mutations have been shown to be loss-of-function, but the functional effects of others (such as p. His76Gln and p. Glnl07Leu) are not known, and may in fact be rare familial variants, A = Alobar; L = lobar; mat = maternal; mic = microform; N/A = not applicable; pat = paternal; S = semilobar; U = unknown.

^aEach family is listed with a different number; individuals within each family are given a different letter.

^bThe form of HPE is described as 'unknown' for patients with no available neuroimaging or with insufficient information for classification.

^cFunctional data derived from El-Jaick et al. [2007].