Supplementary Table 2. Clinically relevant gains and patients’ phenotypes
A. First cohort
Nr
1
Gain
Size Origin
(location)
(kb)
1p34.1-p33
649 de novo
(45862062-
Phenotype
Clinical relevance
Low birth weight (<P3), microcephaly (-5SD),
Duplication includes POMGNT1.22 Phenotype
coloboma, laryngomalacia, severe DD, hypotonia
is comparable to published patients with
duplications including POMGNT1.23-27
46510920)
2
3
4
1q21.1
1,401 maternal
Low birth weight (<P3), short stature (<P3),
(144973941-
epicanthal folds, large ears, deafness, severe
146374685)
brachydactyly, mild DD
Short stature (<P3), long face, blepharophimosis,
Phenotype comparable to previously published
(79084140-
dysplastic ears, syndactyly digits 2-3, moderate
patient with larger duplication.28
86039297)
DD
3p12.3-p12.1
5q31.2
6,955 maternal
Known syndrome.19
288 paternal
Hypertelorism, wide mouth, coarctatio aortae
Phenotype partially comparable to published
(138126593-
patient with larger duplication (mosaic) and
138414724)
heart defect.29
5
6
Short stature (<P3), epicanthal folds,
Duplication includes TWIST. Phenotype is
(18981705-
hypotelorism, low nasal bridge, moderate speech
partially comparable to published patients, with
19359026)
delay, mild hypotonia
duplications including TWIST.30,31
Mild DD, PDD-NOS, mild hypotonia
Partially overlapping phenotype with patients
7p21.1
11q13.3
377 paternal
514 maternal
reviewed by Jehee et al.32
(6925610869770247)
7
15q11.2-
5,348 de novo
Autism, mild DD
Known syndrome.33
Polymicrogyria, epilepsy, segmental NF1, DD,
Known syndrome.34
q13.1
(2085147826199195)
8
16p11.2
578 unknown
(29527989-
behavioural problems
30106253)
9
22q11.21
375 paternal
Short stature (<P3), microcephaly (<P3),
(17809443-
epicanthus, retrognathia, nasal speech, moderate
18184866)
DD
Known syndrome.20
10
22q11.21
2,561 de novo
(17274634-
Moderate DD, behavioural problems (ADHD and
Known syndrome.20
PDD-NOS)
19835557)
11
22q11.21
2,561 paternal
(17274634-
Clinodactyly digit 5, speech delay, mild motor
Known syndrome.20 This patient also had a
delay, mild behavioural problems
47,XYY karyotype and a 452 kb del 15q11.2
19835557)
(chr15:20316791-20769095). Both may have
contributed to the phenotype.35,36
12
22q11.21
2,617 maternal
(17274634-
Preauricular pits, tongue protrusion,
Known syndrome.20 A diagnosis of Beckwith-
polycythemia, nasal nevus flammeus
Wiedemann syndrome was molecularly
19891669)
13
Xp22.2-
confirmed in this patient (imprinting defect).
7,912 maternal
p22.12
Elongated hypotonic face, preauricular pit, low set Duplication is known to cause DD and facial
dysplastic left ear, DD
dysmorphism.37,38
Moderate DD, epilepsy in childhood. No features
In this patient a 45,X[3]/46,XX [7] karyotype
(male)
(1305590420967799)
14
Xp22.31
1,625 de novo
of Turner syndrome were present.
(female)
15
was present. The duplication was present in all
(6467202-
cells and the phenotype is comparable to a
8091950)
previously published boy.39
Low birth weight (<P3), dysmyelination on
Known syndrome, duplication includes
(male)
cerebral MRI, laryngomalacia, DD, breath
MECP2.21
(152773600-
holding spells, hypertonia, autonomic and muscle
153262506)
tone dysregulation
Xq28
489 maternal
B. Second cohort
Nr
16
17
Gain
Size
Phenotype
Clinical relevance
(location)
(kb)
1p22.3-p22.2
6,669 de novo
Growth retardation, large anterior fontanel,
Patient also has also del 1p36 (chr1:2228191-
(84760501-
prominent forehead, deep-set eyes, midface
4455447) that explains most symptoms. It is
91429188)
hypoplasia, prominent chin, brachymeso-
unsure how much the gain contributed to the
phalangy V bilateral, 2 epidermoid cysts (skull)
phenotype, but it is unlikely to be benign.
Short stature, hypertelorism, down slant, ptosis,
Overlapping duplications in Decipher database
1q21.1
Origin
848 unknown
(144093518-
high narrow palate, thin lips, simean crease right
in patients with DD and autism, and in Mefford
144941039)
hand, severe DD, hypotonia, autism, self-
et al.19
injurious behaviour, epilepsy,
18
7q11.23
1,722 unknown
DD, amenorrhea
Known syndrome.40
1,340 de novo
Tall stature, hypertelorism, mild DD, behavioural
Known syndrome.40
(7205848073780403)
19
7q11.23
(72058480-
problems (PDD-NOS)
73398388)
20
12q11-q12
6,775 de novo
(36269652-
Broad forehead, frontal cow-lick, DD, speech
Conventional karyotyping revealed a non-
delay
mosaic marker chromosome 12(q10q12). See:
43044456)
21
22
http://www.med.uni-jena.de/fish/sSMC/
Cleft palate, cleft tongue, milia, notch in lower
Known syndrome41. Also a diagnosis of oral-
(28440968-
lip, syndactyly fingers and toes 2-3, pre-axial
facial-digital syndrome 1 was molecularly
30649058)
polydactyly foot, small VSD, renal cysts
confirmed (mutation in OFD1)
Periorbital fullness, full lips, maxillary dental
Known syndrome41.
15q13.2-q13.3
15q13.2-q13.3
2,208 maternal
1,579 paternal
23
24
(28718935-
overbite, mild DD, behavioural problems (PDD-
30298295)
NOS)
Hypertonia, cerebral edema, contractures, sliding
Similar duplications in Decipher database, may
(28732094-
hernia, feeding problems, respiratory
have contributed to the phenotype, however,
28952417)
insufficiency, soft skin, congenital muscular
unlikely to explain the congenital muscular
dystrophy, died at the age of 4 months
dystrophy.
DD (mild), nasal speech , orofacial muscle
Similar duplications in Decipher database.
16p11.2
16p11.2
220 de novo
220 maternal
(28732094-
weakness, short philtrum, autistic features
28952417)
25
26
16p11.2
606 unknown
Hypertelorism, upslant palpebral fissures,
(29500083-
strabism, featureless philtrum, thin upper lip,
30106253)
broad nasal tip, mild DD, epilepsy, PDD-NOS
16p13.11p12.1
(1516398618214506)
3,050 maternal
Dysplastic ears, moderate DD, autism,
Known syndrome.42
Known syndrome.43
27
16p13.11-
3,440 unknown
Unilateral renal agenesis, low-normal IQ
Known syndrome.43 Patient is also known with
p12.3
velocardiofacial syndrome due to proven
(15159067-
maternally inherited deletion 22q11
18599698)
28
16q23
462 de novo
(74558570-
Prominent forehead, epicanthal folds, mild DD,
CNTNAP4, partly located in duplication; may
ADHD, PDD-NOS
result in disfunctional neurexin. Mutations in
75020751)
neurexins have been associated with autism and
mental retardation.44
29
30
31
Moderate DD, hyperkinetic extra-pyramidal
Patient with similar duplication and hypotonia
(21997814-
movement disorder, hypotonia, oculomotor
and developmental delay published by
23326360)
apraxia, speech delay
Shimojima et al.45
Prominent forehead, hypertelorism, downslant
Duplication includes ATRX and is known to
(female)
palpebral fissures, downturned corners mouth,
result in severe DD and hypotonia in male
(73628980-
simean crease, strabism, reduced visual acquity,
patients. Female carriers can be normal or
77924154)
mild DD, hypotonia
mildly affected.46.
Synophris, thin upper lip, strabism, severe DD,
Known syndrome, duplication includes
22q11.23
Xq13.2-q21.1
Xq28
1,329 maternal
4,295 de novo
489 maternal
(male)
epilepsy, spastic paraplegia, absent speach,
(152773600-
autism
MECP2.21
153262506)
DD = Developmental Delay, MRI=magnetic resonance imaging, NF1= Neurofibromatosis 1, ADHD= Attention-Deficit / Hyperactivity
Disorder, PDD-NOS = Pervasive Developmental Disorder-Not Otherwise Specified
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