Table S6. Genes mutated in human cortical malformations and differentially expressed
between ferret SG and LS
Human cortical malformations were listed as in Barkovich et al (2012). PH = classical
bilareral periventricular heterotopia, LCH = Lissencephaly with cerebellar hypoplasia, MEB
= Muscle–eye–brain disease, ACC = Agenesis of the corpus callosum, PMG = microcephaly
and polymicrogyria, ILS = Isolated lissencephaly sequence, SBH = Subcortical band
heterotopia, WWS = Walker_Warburg Syndrome, AD = autosomal dominant inheritance;
AR = autosomal recessive inheritance; CBLH = cerebellar hypoplasia; CDG = congenital
disorders of glycosylation; CHIME = coloboma, heart defect, ichthyosiform dermatosis,
mental retardation, ear anomalies; CMD = congential muscular dystrophy; CMV =
cytomegalovirus; COB = cobblestone complex; DD/ID = developmental delay/intellectual
disability; DNET = dysembryoplastic neuroepithelial tumour; FCMD = Fukuyama congenital
muscular dystrophy; HMEG = hemimegalencephaly; IUGR = intrauterine growth retardation;
LIS = lissencephaly; MACS = macrocephaly, alopecia, cutis laxa, scoliosis; MAP =
microcephaly with asymmetric polymicrogyria; MCPH = autosomal recessive primary
microcephaly; MDP = microcephaly with diffuse polymicrogyria; MEG = megalencephaly;
MIC = microcephaly; MLIS = microcephaly with lissencephaly; MOPD = microcephalic
osteodysplastic primordial dwarfism syndrome; MPPH = megalencephaly with
polymicrogyria, polydactyly and hydrocephalus; PEHO = progressive encephalopathy with
oedema, hypsarrhythmia and optic atrophy; PLH = periventricular laminar heterotopia;
PMSE = polyhydramnios, megalencephaly and symptomatic epilepsy; PNH = periventricular
nodular heterotopia; SIMP = simplified gyral pattern; XL = X-linked inheritance; XLAG =
X-linked lissencephaly with agenesis of corpus callosum and ambiguous genitalia
OSVZ
FoldChange
Malformation
Reference
AHI1
1.64
Joubert syndrome with variable (low penetrance)
PMG and AHI1 mutations at 6q23.3
ARFGEF2
1.51
PH with microcephaly
ASPM
1.66
Microcephaly vera
ATR
1.73
Seckel syndrome
CDC6
1.77
Bicknell et al. (2011a)
CDK5
1.65
MOPD type 1 with mutations in CDC6 at
17q21.2
Knockout with reeler-like cortex
CDK5RAP2
1.50
Microcephaly vera
CENPJ
1.72
Microcephaly vera. Seckel syndrome
CEP152
1.41
Microcephaly vera
CNTNAP2
1.84
DAB1
1.98
Pitt–Hopkins-like syndrome with mutations of
CNTNAP2 at 7q35-q36
LCH? (predicted, based identical to on
similarity of reeler and scrambler mice)
Thornton and Woods
(2009)
Thornton and Woods
(2009)
Thornton and Woods
(2009)
Zweier et al. (2009)
Dixon-Salazar et al.
(2004); Valente et al.
(2006)
Sheen et al. (2004)
Thornton and Woods
(2009)
O’Driscoll et al. (2003)
Gilmore et al. (1998)
Sheldon et al. (1997)
EOMES
3.07
ACC and PMG
Baala et al. (2007)
ETFA
1.56
Govaert et al. (2004)
ETFB
1.46
FGFR3
2.38
FKRP
1.74
Multiple Acyl-CoA dehydrogenase deficiency
(Glutaric aciduria type II) with mutations of
ETFA at 15q24.2-q24.3
Multiple Acyl-CoA dehydrogenase deficiency
(Glutaric aciduria type II) with mutations of
ETFA at 15q24.2-q24.3
Thanatophoric dysplasia or Apert syndrome with
mutation of FGFR3 at 4p16.3 (six-layered PMGlike cortex)
MEB or WWS
FLNA
1.93
PH
Parrini et al. (2006)
FMR1
1.30
PH with fragile-X syndrome
Moro et al. (2006)
GCSH
1.42
Hamosh A, et al. (1993)
GPC3
4.80
HIP1
8.88
Non-ketotic hyperglycinaemia with mutations of
GCSH at 16q23.2
Simpson–Golabi–Behmel syndrome 1 with
mutations in GPC3 at Xq26.2
PNH and Williams syndrome with deletion
7q11.23, including HIP1
KIAA1279
1.69
Goldberg–Shprintzen syndrome
Brooks et al. (2005)
LARGE
2.23
MEB
Longman et al. (2003)
MECP2
2.29
Amir et al. (1999)
MYCN
1.99
NDE1
1.62
Rett syndrome with mutations of MECP2 at
Xq28
MEG, thumb anomalies and Weaver-like
dysmorphism with dup 2p24.3 (includes
MYCN) Genetically defined with AR
inheritance
MCPH, MDP with mutations in NDE1 at
16p13.11
NRXN1
1.51
Pitt–Hopkins like syndrome with mutations of
NRXN1 at 2p16.3
Zweier et al. (2009)
NSD1
1.36
Türkmen et al. (2003)
NSDHL
1.32
OFD1
2.54
Sotos syndrome with mutations in NSD1 at
5q35.2–q35.3
Perisylvian PMG, mild MIC and thin body
habitus with NSDHL mutation at Xq28
Simpson–Golabi–Behmel syndrome 2 with
mutations in OFD1 at Xp22.2
ORC4
1.44
MOPD type 1 with mutations in ORC4 at 2q22q23
Guernsey et al. (2011)
ORC6
1.56
MOPD type 1 with mutations in ORC6 at 16q12
PAFAH1B1
1.82
ILS or SBH
Bernal and Venkitaraman
(2011)
Cardoso et al. (2002)
POMGNT1
1.29
MEB
PTEN
1.29
RAB3GAP1
2.65
Bannayan–Riley–Ruvalcaba syndrome, Cowden
disease and MEG–autism with mutations in
PTEN at 10q23.31
Micro syndrome
Govaert et al. (2004)
Hevner, (2005)
Beltran-Valero de
Bernabé et al. (2004)
Pilia et al. (1996)
Ferland et al. (2006)
Kaczala et al. (2007)
Alkuraya et al. (2011);
Bakirciogluet al. (2011)
McLarren et al. (2010)
Budny et al. (2006)
Beltrán-Valero de
Bernabé et al. (2002)
Marshet al.(1997); Marsh
et al.,(1999); Pilarski et al.
(2011)
Aligianis et al. (2005)
RAB3GAP2
1.62
Warburg Micro syndrome with mutations of
RAB3GAP2 at 1q41
Pontocerebellar hypoplasia with mutations of
RARS2 at 6q16.1
Frontal predominant mild LIS with severe
hippocampal and CBLH with RELN mutation at
7q22
Amish lethal microcephaly associated with
mutations in SLC25A19 at 17q25.1
Borck et al. (2011)
RARS2
1.80
RELN
1.32
SLC25A19
1.43
SLC9A6
1.62
Angelman-like syndrome with mutations of
SLC9A6 at Xq26.3
Gilfillan et al. (2008)
SNAP29
1.44
CEDNIK syndrome
Sprecher et al. (2005)
SRD5A3
1.66
STIL
1.37
CHIME-like syndrome with frontal predominant
COB with SRD5A3 mutation at 4q12
Microcephaly vera
Al-Gazali et al. (2008);
Cantagrelet al. (2010)
Thornton and Woods
(2009)
STRADA
1.71
Puffenberger et al. (2007)
TCF4
1.50
PMSE syndrome with MEG, cortical dysgenesis
including leptomeningeal glioneuronal
heterotopia and cortical dyslamination with
mutations in STRADA (LYK5)
Pitt–Hopkins syndrome with mutations of TCF4
at 18q21.1
TMEM216
1.46
Valente et al. (2010)
TSC1
1.61
Meckel–Gruber syndrome with variable (low
penetrance) PMG and TMEM216 mutations at
11q12.2
Tuberous sclerosis with cortical hamartomas and
mutations of TSC1 at 9q34.13
TSC2
1.71
Tuberous sclerosis with cortical hamartomas and
mutations of TSC2 at 16p13.3
TSEN54
1.32
Pontocerebellar hypoplasia with mutations of
TSEN54 at 17q25.1
TSEN34
1.86
Namavar et al. (2011)
UBA2
1.32
Pontocerebellar hypoplasia with mutations of
TSEN34 at 19q13.4
XLAG with temporal-posterior predominant LIS
and ACC with mutations in ARX ( UBA2)at
Xp22.13
ISVZ
FoldChange
Malformation
Reference
ASPM
1.61
Microcephaly vera
CDC6
1.48
CDK5
1.31
MOPD type 1 with mutations in CDC6 at
17q21.2
Knockout with reeler-like cortex
CEP152
0.75
Microcephaly vera
DAB1
1.48
LCH? (predicted, based identical to on
similarity of reeler and scrambler mice)
Namavar et al. (2011)
Hong et al. (2000)
Rosenberg et al. (2002)
Zweier et al. (2007)
Jones et al. (1999);
Dabora et al. (2002) );
Crino et al. (2006)
Jones et al. (1999);
Dabora et al. (2002) );
Crino et al. (2006)
Namavar et al. (2011)
Bonneau et al. (2002)
Thornton and Woods
(2009)
Bicknell et al. (2011a)
Gilmore et al. (1998)
Thornton and Woods
(2009)
Sheldon et al. (1997)
ETFDH
0.71
Multiple Acyl-CoA dehydrogenase deficiency
(Glutaric aciduria type II) with mutations of
ETFDH at 4q32.1
PH with fragile-X syndrome
Govaert et al. (2004)
FMR1
0.75
HIP1
0.69
PNH and Williams syndrome with deletion
7q11.23, including HIP1
MEB
Ferland et al. (2006)
LARGE
0.68
MYCN
1.27
MEG, thumb anomalies and Weaver-like
dysmorphism with dup 2p24.3 (includes MYCN)
Genetically defined with AR inheritance
MCPH, MDP with mutations in NDE1 at
16p13.11
Kaczala et al. (2007)
NDE1
1.30
NRXN1
0.62
Zweier et al. (2009)
1.40
Pitt–Hopkins like syndrome with mutations of
NRXN1 at 2p16.3
MOPD type 1 with mutations in ORC6 at 16q12
ORC6
PCNT
0.80
Microcephalic osteodysplastic dwarfism
Bernal and Venkitaraman
(2011)
Griffith et al. (2008)
POMT2
0.76
MEB or WWS
van Reeuwijk et al. (2005)
RAB18
0.64
Bem et al. (2011)
RAB3GAP2
0.59
SRD5A3
1.66
Warburg Micro syndrome with mutations of
RAB18 at 10p12.1
Warburg Micro syndrome with mutations of
RAB3GAP2 at 1q41
CHIME-like syndrome with frontal predominant
COB with SRD5A3 mutation at 4q12
STIL
1.27
Microcephaly vera
TCF4
1.43
TSEN34
0.80
TUBA8
0.70
Pitt–Hopkins syndrome with mutations of TCF4
at 18q21.1
Pontocerebellar hypoplasia with mutations of
TSEN34 at 19q13.4
Polymicrogyria with optic nerve hypoplasia
Thornton and Woods
(2009)
Zweier et al. (2007)
TUBB2B
0.72
YWHAG
1.26
VZ
FoldChange
ASPM
1.36
Microcephaly vera
ATP6V0A2
1.34
Debré-type cutis laxa with frontal predominant
COB and ATP6V0A2 mutation at 12q24.3
CASK
1.27
Najm et al. (2008)
CDC6
1.57
CNTNAP2
0.69
DAB1
1.79
X-linked MIC with disproportionate cerebellar
hypoplasia with mutations of CASK at Xp11.4
(in females)
MOPD type 1 with mutations in CDC6 at
17q21.2
Pitt–Hopkins-like syndrome with mutations of
CNTNAP2 at 7q35-q36
LCH? (predicted, based identical to on similarity
of reeler and scrambler mice)
FMR1
0.70
PH with fragile-X syndrome
Moro et al. (2006)
Fronto-parietal PMG, variable ACC and delayed
myelination of anterior limb internal capsule
with TUBB2B mutations at 6p25.2
PNH and Williams syndrome with deletion
7q11.23, including YWHAG
Malformation
Moro et al. (2006)
Longman et al. (2003)
Alkuraya et al. (2011);
Bakirciogluet al. (2011)
Borck et al. (2011)
Al-Gazali et al. (2008);
Cantagrelet al. (2010)
Namavar et al. (2011)
Abdollahi et al. (2009)
Jaglin et al. (2009)
Ramocki et al. (2010)
Reference
Thornton and Woods
(2009)
Kornak et al. (2008); Van
Maldergem et al. (2008)
Bicknell et al. (2011a)
Zweier et al. (2009)
Sheldon et al. (1997)
GPR56
1.76
Bilateral fronto-parietal cobblestone
malformation (previously polymicrogyria)
Piao et al. (2005)
LARGE
0.71
MEB
Longman et al. (2003)
MYCN
1.81
Kaczala et al. (2007)
NRXN1
0.60
PAX6
1.30
RAB18
0.66
RAB3GAP2
0.78
RELN
0.69
RIN2
0.62
TCF4
1.50
TSC2
0.44
MEG, thumb anomalies and Weaver-like
dysmorphism with dup 2p24.3 (includes MYCN)
Genetically defined with AR inheritance
Pitt–Hopkins like syndrome with mutations of
NRXN1 at 2p16.3
Aniridia, variable temporal PMG, absent anterior
commissure and pineal gland, and variable
CBLH with PAX6 mutations at 11p13
Warburg Micro syndrome with mutations of
RAB18 at 10p12.1
Warburg Micro syndrome with mutations of
RAB3GAP2 at 1q41
Frontal predominant mild LIS with severe
hippocampal and CBLH with RELN mutation at
7q22
MACS syndrome with mutations in RIN2 at
20p11.23
Pitt–Hopkins syndrome with mutations of TCF4
at 18q21.1
Tuberous sclerosis with cortical hamartomas and
mutations of TSC2 at 16p13.3
TUBA1A
1.51
ILS or SBH
Zweier et al. (2009)
Mitchell et al. (2003);
Graziano et al. (2007)
Bem et al. (2011)
Borck et al. (2011)
Hong et al. (2000)
Basel-Vanagaite et al.
(2009)
Zweier et al. (2007)
Jones et al. (1999);
Dabora et al. (2002) );
Crino et al. (2006)
Poirier et al. (2007)