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Supplemental Table: Clinical Findings in Probands and Family Members with TGIF alterations







Patient Mutation, HPE Mic Sz Hypopit. Hypotelorism Hypertelorism NPAS Midface Cleft SCMI Additional Extra-neuro Reference

Protein Type flattening L/P Craniofacial findings

alteration Findings

c.83C>G, + - - + - + - - + Agenesis CC - Gripp et al

1a p.S28C Mic 2000.

c.83C>G, - - - + - - - - - - - Gripp et al

1b p.S28C Mic 2000.

c.83C>G, - - - + - - - - - - - Gripp et al

1c p.S28C Mic 2000.

c.91G>C, + - - - - + - - + - -

2a p.A31P U This report

c.91G>C, - - - - - - - - - - -

2b p.A31P None This report

c.132G>T, + - - - - - + + - Hyperthermia -

p.K44N Breathing diff.

Maxillary Richieri-

hypoplasia Costa et al

3a L Large ears 2008

c.132G>T, - - - - - - - - - - - Richieri-

p.K44N Costa et al

3b None 2008

c.133G>T, + + + - - - + + - Abnormal -

p.E45X ventricles,

hypothalamic and El-Jaick at al

4 L caudate fusion, 2007

c.228C>A, ? ? ? ? ? ? ? ? ? ? ? El-Jaick at al

5 p.H76Q U 2007

c.140_141de + - + - - - + + - Dystonia -

lTG/c.228C> Absent olfactory

A, tracts, premaxillary

p.S46fs, dysgensis El-Jaick at al

6a p.H76Q S 2007

c.228C>A, - - - - - - - - - Hypothyroidism - El-Jaick at al

6b p.H76Q None 2007

c.140_141de - - - - - - - - - Hypothyroidism -

lTG, El-Jaick at al

6c p.S46fs None 2007

c.177C>G, + - - + - - + - - Cebocephaly - Aguilella et

7a p.Y59X S turricephaly al 2003 .

c.177C>G, - - - + - - - + - - - Aguilella et

7b p.Y59X Mic al 2003 .

c.187C>G, - - + - - - - + - - - Gripp et al

8 p.P63R L 2000.

c.257delT, ? ? ? ? ? ? ? ? ? ? ?

9a p.F86fs A This report

Supplemental Table: Clinical Findings in Probands and Family Members with TGIF alterations







c.257delT, - - - - - - - - - - -

9b p.F86fs None This report

c.268C>T, + ? ? + - - + + ? Brachycephaly - Chen CP et al

10 p.R90C A 2002

c.271C>T, ? - ? ? ? ? + ? ? - -

11a p.R91C S This report

c.271C>T, ? - ? ? ? ? + ? ? - -

11b p.R91C A This report

c.271C>T, - - - - - - - - - - -

11c p.R91C None This report

c.320A>T, ? ? ? ? ? ? ? ? ? ? ? Aguilella et

12a p.Q107L U al 2003

c.320A>T, + - - - - - - + - Mental retardation - Aguilella et

p.Q107L al 2003; El-

Jaick et al.,

12b U 2008

c.388T>C, - - - + - - - - - - - Chen M et al

13a p.V126A L 2006.

c.388T>C, ? ? ? ? ? ? ? ? ? ? ? Chen M et al

13b p.V126A S 2006.

c.388T>C, ? ? ? ? ? ? ? ? ? ? ? Chen M et al

13c p.V126A L 2006.

c.388T>C, - - - + - - - - - Circle of Willis - Chen M et al

13d p.V126A Mic anomalies 2006.

c.436G>T,p. ? ? ? ? ? ? ? ? ? ? ?

14 A146S U This report

c.451C>G, + - - + - - + + - - -

p.T151A

(SHH:

c.1283_1291

del, Nanni et al.,

p.378_380de 1999; Gripp

15 l) S et al 2000.

c.485C>T, - - - - + - - + - Ethmoidal and -

p.S162F sphenoidal Gripp et al

encephaloceles; 2000.; El-

Agenesis CC Jaick et al

16a Mic 2007

c.485C>T, - - - - - - - - - - - Gripp et al

16b p.S162F None 2000.

c.778delC, ? ? ? ? ? ? ? ? ? ? ? El-Jaick et al

17a p.K259fs U 2007

c.778delC, - - - + - - - - - Anosmia - El-Jaick et al

17b p.K259fs Mic 2007

c.778delC, - + + - - + - - - Ectopic posterior GERD

18 p.K259fs L pituitary This report

Supplemental Table: Clinical Findings in Probands and Family Members with TGIF alterations







Small optic nerves

Gene - + + - - - - + - Schizencephaly -

deletion Optic hypoplasia Bendavid et

19 (FISH) A al., 2006

Gene ? ? ? ? ? ? ? ? ? ? ?

deletion Bendavid et

20 (MLPA) S al., 2009

del(18)(p111 + ? - + - + + + - - -

.23pter)

(SHH:

c.1270C>G, Nanni et al.,

21 p.P424A) S 1999

del(18)(p11. + - + - + + + - + Ectopic post. 5th finger

318pter) Pituitary clinodactyly Portnoi et al,

22a Mic Diffuse hypotonia 2007

del(18)(p11. + - - - - - + - + Nasal obstruction -

318pter) managed with Portnoi et al,

22b Mic surgery 2007

del(18)(p11. ? ? ? - - - - ? ? Arrhinencephaly TOF, uterus

118pter) Proboscis and vagina

Iris colobomata duplex,

synophthalmia syndactylia Kuchle et al,

23 U 1991

del(18)(p11 - - - - - - + - + Dolichocephaly 5th finger

18pter) Uplanting palpebral clinodactyly,

fissures with syndactyly of

epicanthal folds, toes

prom. Median

palatal raphe, Morales-

dental carries, large Peralta, et al,

24 Mic ears 1983

del(18)(p11 ? ? + ? ? ? ? ? + ? ? Boudailliez

25 18pter) U et al, 1983

del(18)(p) + - - - + - + + - Muscular Broad chest

(1/2 of 18p) hypotonia,

microretrognathia,

large protruding Faust et al,

26 U ears 1976

del(18)(p) + ? ? + - ? + + ? Arrhinencephaly VSD,

(3/4 of 18p) ,missing inferior malformation

vermis of of spleen

cerebellum, Faust et al,

27 L muscular hypotonia 1976

del(18)(p) ? - - - - - - - + Long philtrum, 5th finger

small nose, thick clinodactyly, Aughton et

28 Mic pinnae single al, 1991

Supplemental Table: Clinical Findings in Probands and Family Members with TGIF alterations







transverse

palmar

creases

del(18)(p) - - - - - - - - + Downslanting

palpebral fissures,

epicanthal folds,

torus palatinus,

nose with short

columnella and Dolan et al,

29 Mic hypoplastic alae 1981

arr(18): + ? + ? ? ? ? + ? ?

140,284- “Midline defects” Rosenfeld et

30 14,065,199 L al., 2010

arr(18): chr + ? _ _ _ _ _ _ _ _ ?

18: 5,982- Rosenfeld et

31 14,065,199 Mic al., 2010

arr(18): chr + ? - - - - - - - - ?

18: 5,982- Rosenfeld et

32 14,065,199 Mic al., 2010

arr(18): - ? - - - - - + - - ?

102,328- Rosenfeld et

33 15,079,388 Mic al., 2010

arr(18): - ? - + - - - + - - ?

140,284- Rosenfeld et

34 10,600,909 Mic al., 2010

arr(18): ? ? ? ? ? ? ? ? ? ? ?

5,982- Rosenfeld et

35 4,974,551 U al., 2010

arr(18): + ? + - - - - - + Bifid uvula ?

5,982- Rosenfeld et

36 4,974,551 Mic al., 2010

Del(18)(p11. ? - ? ? ? - + - ? Proboscis - Sepulveda et

37 2pter) A al., 2009

Gene ? ? ? ? ? ? ? ? ? ? ?

deletion

38 (aCGH) Mic This report



CC: Corpus Callosum; GERD: Gastroesophageal reflux disease; M: Microcephaly ; S: Seizures; Hypopit: Hypopituitarism; NPAS: Nasal Pyriform Aperature Stenosis; SCMI: Single Central Maxillary

Incisor; TOF: Tetralogy of Fallot; VSD: Ventricular Septal Defect



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