MCID: CHR662
MIFTS: 42

Chromosome 15q13.3 Deletion Syndrome

Categories: Fetal diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Chromosome 15q13.3 Deletion Syndrome

MalaCards integrated aliases for Chromosome 15q13.3 Deletion Syndrome:

Name: Chromosome 15q13.3 Deletion Syndrome 56 52 25
Chromosome 15q13.3 Microdeletion Syndrome 56 12 52 36 13 43 15
15q13.3 Microdeletion Syndrome 12 52 25 58 29 6
15q13.3 Microdeletion 24 52 25
Microdeletion 15q13.3 Syndrome 52
Monosomy 15q13.3 58
Del(15)(q13.3) 58

Characteristics:

Orphanet epidemiological data:

58
15q13.3 microdeletion syndrome
Inheritance: Autosomal dominant,Not applicable; Age of onset: Childhood;

HPO:

31
chromosome 15q13.3 deletion syndrome:
Inheritance autosomal dominant inheritance
Onset and clinical course incomplete penetrance


GeneReviews:

24
Penetrance The penetrance of the 15q13.3 microdeletion is highly variable....

Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


Summaries for Chromosome 15q13.3 Deletion Syndrome

Genetics Home Reference : 25 15q13.3 microdeletion is a chromosomal change in which a small piece of chromosome 15 is deleted in each cell. The deletion occurs on the long (q) arm of the chromosome at a position designated q13.3. This chromosomal change increases the risk of intellectual disability, seizures, behavioral problems, and psychiatric disorders. However, some people with a 15q13.3 microdeletion do not appear to have any associated features. About half of all people with a 15q13.3 microdeletion have learning difficulties or intellectual disability, which is usually mild or moderate. Many of these individuals have delayed speech and language skills. 15q13.3 microdeletion also appears to be a major risk factor for recurrent seizures (epilepsy); about one-third of people with this chromosomal change have epilepsy. 15q13.3 microdeletion has also been associated with behavioral problems, including a short attention span, aggression, impulsive behavior, and hyperactivity. Some people with a 15q13.3 microdeletion have been diagnosed with developmental disorders that affect communication and social interaction (autism spectrum disorders). This chromosomal change may also be associated with an increased risk of psychiatric disorders, particularly schizophrenia. Other signs and symptoms of 15q13.3 microdeletion can include heart defects, minor abnormalities involving the hands and arms, and subtle differences in facial features. Some people with a 15q13.3 microdeletion do not have any of the intellectual, behavioral, or physical features described above. In these individuals, the microdeletion is often detected when they undergo genetic testing because they have an affected relative. It is unknown why a 15q13.3 microdeletion causes cognitive and behavioral problems in some individuals but few or no health problems in others.

MalaCards based summary : Chromosome 15q13.3 Deletion Syndrome, also known as chromosome 15q13.3 microdeletion syndrome, is related to epilepsy, idiopathic generalized and angelman syndrome. An important gene associated with Chromosome 15q13.3 Deletion Syndrome is DEL15Q13.3 (Chromosome 15q13.3 Microdeletion Syndrome). The drugs Acetylcholine and Nicotine have been mentioned in the context of this disorder. Affiliated tissues include heart and testes, and related phenotypes are intellectual disability and global developmental delay

Disease Ontology : 12 A chromosomal deletion syndrome that is characterized by intellectual dsability, developmental delay, autism spectrum disorder and seizure, has material basis in autosomal dominant inheritance of partial deletion of the long arm of chromosome 15.

NIH Rare Diseases : 52 15q13.3 microdeletion syndrome is a genetic disorder caused by a deletion of several genes on chromosome 15 . When a syndrome is caused by the deletion of several genes, it is also known as a microdeletion syndrome or a contiguous gene deletion syndrome. Individuals with 15q13.3 microdeletion syndrome may have very different signs and symptoms from other affected individuals (even within the same family), or no symptoms at all. Features of the condition may include mild to moderate intellectual disabilities , learning delays, or normal intelligence; autism spectrum disorders; epilepsy (recurring seizures ); and mental illness (such as schizophrenia or bipolar disorder). Various dysmorphic (abnormally formed) features have been reported, but there are no consistent physical features among individuals who have the condition. 15q13.3 microdeletion syndrome is caused by a deletion on the long arm of chromosome 15 that spans at least 7 genes and usually includes the CHRNA7 gene. It can be inherited in an autosomal dominant manner with reduced penetrance , or can occur as a new (de novo ) deletion. Treatment typically focuses on individual signs and symptoms when possible.

OMIM : 56 Heterozygous deletion of chromosome 15q13.3 is associated with a highly variable phenotype, even within families segregating the same deletion. Individuals with the deletion may have mild to moderate mental retardation or learning difficulties, or may have no cognitive deficits. Some individuals have epilepsy. Various dysmorphic features have been described, but there is no consistent or recognizable phenotype (review by van Bon et al., 2009). Patients with homozygous deletions in this region have severe neurodevelopmental problems, with epileptic encephalopathy, hypotonia, and poor growth (Endris et al., 2010). (612001)

KEGG : 36 Chromosome 15q13.3 microdeletion syndrome causes a spectrum of cognitive disorders. The syndrome is caused by microdeletions in the 15q13.2q-13.3 region. This chromosomal region contains seven genes and is flanked by a breakpoint (BP) on each side. About 80% of patients with this syndrome have one or more neuropsychiatric diagnoses, including developmental disability/intellectual disability, autism spectrum disorder, speech problems, and attention deficit hyperactivity disorder (ADHD). The neuropsychiatric phenotypes of 15q13.3 microdeletion syndrome have been proposed to be caused by haploinsufficiency of CHRNA7, which is one of the seven genes.

GeneReviews: NBK50780

Related Diseases for Chromosome 15q13.3 Deletion Syndrome

Diseases related to Chromosome 15q13.3 Deletion Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 40)
# Related Disease Score Top Affiliating Genes
1 epilepsy, idiopathic generalized 30.2 OTUD7A MTMR10 CHRNA7 ARHGAP11B
2 angelman syndrome 29.4 UBE3A NPAP1 NIPA2 APPL1
3 prader-willi syndrome 29.2 UBE3A NPAP1 NIPA2 ARHGAP11A APPL1
4 chromosome 15q11-q13 duplication syndrome 11.4
5 visual epilepsy 10.3
6 hypotonia 10.3
7 seizure disorder 10.3
8 epilepsy, idiopathic generalized 7 10.3
9 west syndrome 10.3
10 mood disorder 10.3
11 tricuspid valve stenosis 10.3 KLF13 CHRNA7
12 pyromania 10.2 MTMR10 CHRNA7 ARHGAP11B
13 autism 10.1
14 alacrima, achalasia, and mental retardation syndrome 10.1
15 autism spectrum disorder 10.1
16 microcephaly 10.1
17 15q duplication syndrome and related disorders 10.1
18 attention deficit-hyperactivity disorder 10.1
19 immunoglobulin e concentration, serum 10.1
20 abnormal hair, joint laxity, and developmental delay 10.1
21 ataxia and polyneuropathy, adult-onset 10.1
22 yemenite deaf-blind hypopigmentation syndrome 10.1
23 congenital stationary night blindness 10.1
24 syndromic intellectual disability 10.1
25 non-syndromic intellectual disability 10.1
26 placenta praevia 10.1
27 epilepsy 10.1
28 night blindness 10.1
29 autosomal recessive congenital stationary night blindness 10.1
30 schizophrenia 10 10.1 TRPM1 OTUD7A MTMR10 KLF13
31 short-rib thoracic dysplasia 1 with or without polydactyly 10.1 TRPM1 MTMR10 FAN1
32 interstitial nephritis, karyomegalic 10.1 MTMR10 FAN1
33 autosomal dominant nocturnal frontal lobe epilepsy 10.0 MTMR10 CHRNA7 CHRFAM7A ARHGAP11B
34 cataract 25 9.9 NIPA2 IGFBP2
35 epilepsy, myoclonic juvenile 9.9 OTUD7A MTMR10 FAN1 CHRNA7 ARHGAP11B
36 benign epilepsy with centrotemporal spikes 9.9 OTUD7A MTMR10 CHRNA7 ARHGAP11B ARHGAP11A
37 chromosome 15q11.2 deletion syndrome 9.8 NIPA2 IGFBP2
38 albinism, oculocutaneous, type ii 9.8 OTUD7A NIPA2
39 pervasive developmental disorder 9.7 UBE3A FAN1 CHRNA7 APPL1
40 chromosomal disease 9.6 UBE3A NPAP1 NIPA2 APPL1

Graphical network of the top 20 diseases related to Chromosome 15q13.3 Deletion Syndrome:



Diseases related to Chromosome 15q13.3 Deletion Syndrome

Symptoms & Phenotypes for Chromosome 15q13.3 Deletion Syndrome

Human phenotypes related to Chromosome 15q13.3 Deletion Syndrome:

58 31 (show all 34)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
2 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
3 abnormal facial shape 31 frequent (33%) HP:0001999
4 macrocephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000256
5 frontal bossing 58 31 occasional (7.5%) Occasional (29-5%) HP:0002007
6 seizures 58 31 very rare (1%) Occasional (29-5%) HP:0001250
7 muscular hypotonia 58 31 very rare (1%) Occasional (29-5%) HP:0001252
8 macrotia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000400
9 short stature 58 31 occasional (7.5%) Occasional (29-5%) HP:0004322
10 downslanted palpebral fissures 58 31 occasional (7.5%) Occasional (29-5%) HP:0000494
11 microcephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000252
12 protruding ear 58 31 occasional (7.5%) Occasional (29-5%) HP:0000411
13 strabismus 58 31 very rare (1%) Occasional (29-5%) HP:0000486
14 epicanthus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000286
15 autism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000717
16 attention deficit hyperactivity disorder 58 31 occasional (7.5%) Occasional (29-5%) HP:0007018
17 melanocytic nevus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000995
18 clinodactyly of the 5th finger 58 31 very rare (1%) Occasional (29-5%) HP:0004209
19 bipolar affective disorder 58 31 occasional (7.5%) Occasional (29-5%) HP:0007302
20 schizophrenia 58 31 occasional (7.5%) Occasional (29-5%) HP:0100753
21 prominent nasal tip 58 31 occasional (7.5%) Occasional (29-5%) HP:0005274
22 abnormality of cardiovascular system morphology 31 very rare (1%) HP:0030680
23 hypertelorism 31 very rare (1%) HP:0000316
24 behavioral abnormality 31 very rare (1%) HP:0000708
25 brachydactyly 31 very rare (1%) HP:0001156
26 intellectual disability, moderate 31 very rare (1%) HP:0002342
27 intellectual disability, mild 31 very rare (1%) HP:0001256
28 intellectual disability, severe 31 very rare (1%) HP:0010864
29 specific learning disability 31 very rare (1%) HP:0001328
30 abnormality of the pinna 31 very rare (1%) HP:0000377
31 synophrys 31 very rare (1%) HP:0000664
32 abnormality of the palpebral fissures 31 very rare (1%) HP:0008050
33 malformation of the heart and great vessels 58 Occasional (29-5%)
34 abnormality of the face 31 HP:0000271

Clinical features from OMIM:

612001

Drugs & Therapeutics for Chromosome 15q13.3 Deletion Syndrome

Drugs for Chromosome 15q13.3 Deletion Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Acetylcholine Approved, Investigational 51-84-3 187
2
Nicotine Approved 54-11-5 942 89594
3 Neurotransmitter Agents
4 Central Nervous System Stimulants
5 Autonomic Agents
6 Cholinergic Agents
7 Nicotinic Agonists

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Effects of Transdermal Nicotine on Response Inhibition to Emotional Cues in Schizophrenia Recruiting NCT03838484 Nicotine Patch, 7 Mg/24 Hr;Placebo patch

Search NIH Clinical Center for Chromosome 15q13.3 Deletion Syndrome

Cochrane evidence based reviews: chromosome 15q13.3 microdeletion syndrome

Genetic Tests for Chromosome 15q13.3 Deletion Syndrome

Genetic tests related to Chromosome 15q13.3 Deletion Syndrome:

# Genetic test Affiliating Genes
1 15q13.3 Microdeletion Syndrome 29 CHRNA7 KLF13

Anatomical Context for Chromosome 15q13.3 Deletion Syndrome

MalaCards organs/tissues related to Chromosome 15q13.3 Deletion Syndrome:

40
Heart, Testes

Publications for Chromosome 15q13.3 Deletion Syndrome

Articles related to Chromosome 15q13.3 Deletion Syndrome:

(show all 41)
# Title Authors PMID Year
1
Delineating the 15q13.3 microdeletion phenotype: a case series and comprehensive review of the literature. 56 24 6
25077648 2015
2
Identification of single gene deletions at 15q13.3: further evidence that CHRNA7 causes the 15q13.3 microdeletion syndrome phenotype. 24 56
22775350 2013
3
Delineation of 15q13.3 microdeletions. 24 56
20236110 2010
4
A small recurrent deletion within 15q13.3 is associated with a range of neurodevelopmental phenotypes. 24 56
19898479 2009
5
Further delineation of the 15q13 microdeletion and duplication syndromes: a clinical spectrum varying from non-pathogenic to a severe outcome. 24 56
19372089 2009
6
Microdeletion 15q13.3: a locus with incomplete penetrance for autism, mental retardation, and psychiatric disorders. 24 56
19289393 2009
7
A 15q13.3 microdeletion segregating with autism. 56 24
19050728 2009
8
Microdeletion/duplication at 15q13.2q13.3 among individuals with features of autism and other neuropsychiatric disorders. 56 24
18805830 2009
9
A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures. 56 24
18278044 2008
10
OTUD7A Regulates Neurodevelopmental Phenotypes in the 15q13.3 Microdeletion Syndrome. 56
29395074 2018
11
Otud7a Knockout Mice Recapitulate Many Neurological Features of 15q13.3 Microdeletion Syndrome. 56
29395075 2018
12
Chrna7 deficient mice manifest no consistent neuropsychiatric and behavioral phenotypes. 56
28045139 2017
13
Palindromic GOLGA8 core duplicons promote chromosome 15q13.3 microdeletion and evolutionary instability. 56
25326701 2014
14
A mouse model that recapitulates cardinal features of the 15q13.3 microdeletion syndrome including schizophrenia- and epilepsy-related alterations. 56
24090792 2014
15
Copy number variants of schizophrenia susceptibility loci are associated with a spectrum of speech and developmental delays and behavior problems. 56
21792059 2011
16
An evidence-based approach to establish the functional and clinical significance of copy number variants in intellectual and developmental disabilities. 56
21844811 2011
17
15q13.3 Microdeletion 6
21290787 2010
18
Homozygous loss of CHRNA7 on chromosome 15q13.3 causes severe encephalopathy with seizures and hypotonia. 56
20979196 2010
19
Penetrance for copy number variants associated with schizophrenia. 56
20587603 2010
20
Support for the involvement of large copy number variants in the pathogenesis of schizophrenia. 56
19181681 2009
21
Population analysis of large copy number variants and hotspots of human genetic disease. 56
19166990 2009
22
Common inversion polymorphisms and rare microdeletions at 15q13.3. 56
18854863 2009
23
The copy number variant involving part of the alpha7 nicotinic receptor gene contains a polymorphic inversion. 56
18545269 2008
24
CNVs conferring risk of autism or schizophrenia affect cognition in controls. 24
24352232 2014
25
Genome-wide analysis of copy number variants in attention deficit hyperactivity disorder: the role of rare variants and duplications at 15q13.3. 24
22420048 2012
26
Structures and molecular mechanisms for common 15q13.3 microduplications involving CHRNA7: benign or pathological? 24
20506139 2010
27
Genome-wide copy number variation in epilepsy: novel susceptibility loci in idiopathic generalized and focal epilepsies. 24
20502679 2010
28
Rare deletions at 16p13.11 predispose to a diverse spectrum of sporadic epilepsy syndromes. 24
20398883 2010
29
Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies. 24
19843651 2010
30
Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance. 24
19592580 2009
31
15q13.3 microdeletions increase risk of idiopathic generalized epilepsy. 24
19136953 2009
32
Rare chromosomal deletions and duplications increase risk of schizophrenia. 24
18668038 2008
33
Large recurrent microdeletions associated with schizophrenia. 24
18668039 2008
34
Recurrent rearrangements in the proximal 15q11-q14 region: a new breakpoint cluster specific to unbalanced translocations. 24
17264869 2007
35
Linkage disequilibrium analysis of the CHRNA7 gene and its partially duplicated region in schizophrenia. 24
17113175 2007
36
Detailed analysis of 15q11-q14 sequence corrects errors and gaps in the public access sequence to fully reveal large segmental duplications at breakpoints for Prader-Willi, Angelman, and inv dup(15) syndromes. 24
17573966 2007
37
Genetics of chromosome 15q13-q14 in schizophrenia. 24
16843094 2006
38
Association study of the human partially duplicated alpha7 nicotinic acetylcholine receptor genetic variant with bipolar disorder. 24
14729237 2004
39
Recent segmental duplications in the human genome. 24
12169732 2002
40
Evaluation of the positional candidate gene CHRNA7 at the juvenile myoclonic epilepsy locus (EJM2) on chromosome 15q13-14. 24
12049804 2002
41
Mouse Model of Chromosome 15q13.3 Microdeletion Syndrome Demonstrates Features Related to Autism Spectrum Disorder. 61
26658876 2015

Variations for Chromosome 15q13.3 Deletion Syndrome

ClinVar genetic disease variations for Chromosome 15q13.3 Deletion Syndrome:

6 ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 CHRNA7 , FAN1 , KLF13 , MIR211 , MTMR10 , OTUD7A , TRPM1 15q13.3deletion Pathogenic 21009 15:31137104-32445408
2 CHRNA7 , FAN1 , KLF13 , MIR211 , MTMR10 , OTUD7A , TRPM1 GRCh37/hg19 15q13.2-13.3(chr15:31108661-32446830)x1copy number loss Uncertain significance 443751 15:31108661-32446830
3 CHRNA7 , FAN1 , KLF13 , MIR211 , MTMR10 , OTUD7A , TRPM1 GRCh37/hg19 15q13.2-13.3(chr15:31108661-32446830)x1copy number loss not provided 441046 15:31108661-32446830

Copy number variations for Chromosome 15q13.3 Deletion Syndrome from CNVD:

7
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 91036 15 27359655 28801860 Deletion APBA2 15q13.3 microdeletion syndrome
2 91037 15 27359655 28801860 Deletion CHRFAM7A 15q13.3 microdeletion syndrome
3 91038 15 27359655 28801860 Deletion CHRNA7 15q13.3 microdeletion syndrome
4 91039 15 27359655 28801860 Deletion FAM189A1 15q13.3 microdeletion syndrome
5 91040 15 27359655 28801860 Deletion FAM7A 15q13.3 microdeletion syndrome
6 91041 15 27359655 28801860 Deletion NDNL2 15q13.3 microdeletion syndrome
7 91042 15 27359655 28801860 Deletion TJP1 15q13.3 microdeletion syndrome

Expression for Chromosome 15q13.3 Deletion Syndrome

Search GEO for disease gene expression data for Chromosome 15q13.3 Deletion Syndrome.

Pathways for Chromosome 15q13.3 Deletion Syndrome

GO Terms for Chromosome 15q13.3 Deletion Syndrome

Cellular components related to Chromosome 15q13.3 Deletion Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 acetylcholine-gated channel complex GO:0005892 8.62 CHRNA7 CHRFAM7A

Biological processes related to Chromosome 15q13.3 Deletion Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 synaptic transmission, cholinergic GO:0007271 8.62 CHRNA7 CHRFAM7A

Molecular functions related to Chromosome 15q13.3 Deletion Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 acetylcholine binding GO:0042166 8.96 CHRNA7 CHRFAM7A
2 acetylcholine receptor activity GO:0015464 8.62 CHRNA7 CHRFAM7A

Sources for Chromosome 15q13.3 Deletion Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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