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. Author manuscript; available in PMC: 2017 Aug 1.
Published in final edited form as: Hum Mutat. 2016 May 25;37(8):804–811. doi: 10.1002/humu.23012

Table 2.

Summary of results for the 11 candidate variants detected by WES in 19 female ID patients with extreme skewing

Patient number XCI pattern Gene
Location Type of variant
Variant Inheritance

NGS-Logistics
XCI pattern mother PhyloP
SIFT
PolyPhen2
LRT
MutationTaster
On Xa or Xi? Escape?
Carrel et al 2005)
Major clinical features

Remarks
Candidate causes XLID and skewing 1 99 mat DDX3X X:41203531 ns NM_001193417.2:
c.856G>A:p.G286S
likely de novo 0/1115 78 C / D D / ? 9/9 Severe ID, ataxic
gait, cleft uvula,
facial dysmorphism,
vesicoureteric reflux
2 92 pat DDX3X X:41202502 stop NM_001193417.2:
c.529G>T:p.G177X
de novo 0/734 52 C / / D / ? 9/9 Mild to moderate ID,
pre- and postnatal
growth restriction, hirsutism,
hypertelorism, facial
features, hallux
valgus with foot
arches
3 93 pat SMC1A X:53430567 ns NM_006306.3:
c.2351T>C:p.I784T
de novo 0/870 76 C D D D D Xi 7/9 Severe psychomotor
delay, intrauterine
and postnatal
growth restriction,
synophrys, hirsutism,
dysmorphism,
microcephaly,
hypertonia,
congenital heart
anomalies,
gastroesophageal
reflux, hearing loss,
hallux valgus, talus
valgus, dysplastic
nails
2 female ID
patients with
skewing and
same variant
(Gervasini et al. 2013;
Limongelli et al. 2010)
4 93 mat WDR45 X:48933072 fr del NM_001029896.1:
c.777delT:p.T260Lfs*27
de novo 0/? 81 / / / / / Xa 0/9 Severe ID,
progressive spasticity,
short stature (145 cm
at 29 years)
5 95 mat NHS X:17705990 stop NM_001136024.3:
c.163C>T:p.Q55X
de novo 0/836 72 C / / D A ? 3/9 Mild ID, ASD,
congenital cataract
microphthalmia,
abnormal teeth
6 94 ? MECP2 X:153296399 stop NM_004992.3:
c.880C>T:p.R294X
0/801 C / / D / ? 0/9 Severe ID, spastic
quadriplegia,
microcephaly (OFC –
3.3)
rs61751362
Candidate causes
skewing
7 98 mat MED12 X:70343021 ns NM_005120.2:
c.1562G>A:p.R521H
de novo 0/811 79 C D D D D Xi 0/9 Severe ID, ASD
8 93 mat HDAC8 X:71681901 ns NM_018486.2:
c.958G>A:p.G320R
de novo 0/711 87 C D P D D Xi NR Moderate ID,
postnatal growth
restriction, hypotonia,
seizures, autistic traits
male patient
with same
variant
(Deardorff et al. 2012)
Candidate
causes
autosomal ID
9 96 ? EP300 22:41574281 in-frame del NM_001429.3:
c.6567_6578del:p.2189_2193del
0/? / / / / / ? / Mild developmental
delay, hearing
disability, relative
microcephaly,
dysmorphism
Candidate
causes
skewing
10 93 ? SYNGAP1
TAF9B
6: 33412306
X:77392414
ns
indel affecting splicing
NM_006772.2:
c.3494C>T:p.S1165L
NG_012570.1:g.7766_7770delinsAA
0/802
0/?
? C T D D D
/ / / / /
? /
0/9
Nonsyndromic mild
to moderate ID,
schizophrenia

X-linked genes are indicated in bold; ID: intellectual disability; XCI: X chromosome inactivation; mat/pat: maternally/paternally inherited predominantly inactivated X chromosome; XLID: X-linked ID; NR: not reported; ns: nonsynonymous; fr: frameshift; del: deletion; ins: insertion; stop: stop variant; C: conserved; /: not applicable; D: damaging/deleterious/disease causing; T: tolerated; P: possibly damaging; A: disease automatic; Xi: inactive X; Xa: active X; ASD: autism spectrum disorder; OFC: occipitofrontal head circumference