15q11.2-q13.1 Copy Number Variation

Description

The 15q11.2-q13.1 copy number variation syndrome can result in the loss or duplication of up to 20 protein-coding genes, leading to widespread effects on human development. This region includes well-studied syndromes such as Prader-Willi and Angelman.

Genomic location

Assembly:

Coordinates:

Disorder Information from Orphanet

ORPHA:739 Deletion syndrome

OMIM: 176270, 615547

Prevalence: 1-9 / 100 000

Definition:

A rare genetic, neurodevelopmental syndrome characterized by hypothalamic-pituitary dysfunction with severe hypotonia and feeding deficits during the neonatal period followed by an excessive weight gain period with hyperphagia with a risk of severe obesity during childhood and adulthood, learning difficulties, deficits of social skills and behavioral problems or severe psychiatric problems.

Phenotypic features:

Obligate (100%)	Very frequent (99–80%)	Frequent (79–30%)	Occasional (29–5%)	Very rare (<4-1%)	Excluded (0%)
-	Cryptorchidism Anxiety Infertility Hypotonia Motor delay Growth delay Dysphagia Short stature Feeding difficulties in infancy Abnormal temper tantrums	Abnormal rapid eye movement sleep Gastroparesis Polyphagia Scoliosis Increased susceptibility to fractures Obstructive sleep apnea External genital hypoplasia Hypopigmentation of hair Accelerated skeletal maturation Enamel hypoplasia Intellectual disability, borderline Attention deficit hyperactivity disorder Decreased testicular size Central sleep apnea Impaired temperature sensition Small pituitary gland Perisylvian polymicrogyria Abdominal obesity Decreased circulating gonadotropin level Reduced circulating growth hormone concentration Small hand Brain imaging abnormality Small scrotum Hypoplastic labia majora Clitoral hypoplasia Hypoplastic labia minora Hypogonadism Abnormality of the dentition Strabismus Hypermetropia Myopia Dental crowding Periodontitis Atypical behavior Delayed speech and language development Primary amenorrhea Delayed puberty Decreased response to growth hormone stimulation test Osteopenia Osteoporosis Edema Hypopigmentation of the skin Erysipelas Intellectual disability, mild Hyporeflexia Specific learning disability Failure to thrive Decreased fetal movement Weak cry Short foot Abnormal facial shape Poor suck Ventriculomegaly Recurrent respiratory infections	Xerostomia Narrow nasal bridge Psychosis Autistic behavior Hypertension Seizure Excessive daytime somnolence Stroke Hip dysplasia Vomiting Gastroesophageal reflux Intellectual disability, moderate Abnormal cerebral white matter morphology Downturned corners of mouth Type II diabetes mellitus Almond-shaped palpebral fissure Pituitary hypothyroidism Nasogastric tube feeding in infancy Adrenocorticotropic hormone deficiency Central hypothyroidism Skin-picking Premature pubarche Premature adrenarche Decreased inhibin B level	Precocious puberty Central adrenal insufficiency	-

ORPHA:72 Deletion syndrome

OMIM: 105830

Prevalence: 1-9 / 100 000

Definition:

A rare genetic neurodevelopmental disorder characterized by moderate to severe intellectual disability, microcephaly, seizures, ataxic gait and distinct abnormal facial shape.

Phenotypic features:

Obligate (100%)	Very frequent (99–80%)	Frequent (79–30%)	Occasional (29–5%)	Very rare (<4-1%)	Excluded (0%)
-	Microcephaly Atypical behavior Autistic behavior Inappropriate laughter Delayed speech and language development Hyperactivity Seizure Ataxia Motor delay Tremor Cerebral cortical atrophy Broad-based gait Abnormality of speech or vocalization EEG abnormality Sleep abnormality Poor speech Intellectual disability, severe Severe global developmental delay Self-injurious behavior	Wide mouth Astigmatism Strabismus Hypopigmentation of the skin Obesity Abnormal facial shape Constipation Gastroesophageal reflux Fair hair Drooling Polyphagia Scoliosis Sleep-wake cycle disturbance Iris hypopigmentation Floppy infant Protruding tongue Abnormality of the gastrointestinal tract Feeding difficulties Recurrent hand flapping	Mandibular prognathia Ptosis Hypermetropia Optic disc pallor Myopia Keratoconus Nystagmus Amblyopia Optic atrophy Widely spaced teeth Aggressive behavior Anxiety Reduced eye contact Myoclonus Absent speech Vomiting Dysphagia Poor suck Generalized myoclonic seizure Status epilepticus Inability to walk Flat occiput Cerebral dysmyelination Atypical absence seizure Pes valgus Precocious puberty in females Atonic seizure Gastrostomy tube feeding in infancy Delayed menarche Happy demeanor Nasogastric tube feeding Tongue thrusting	Infantile spasms	-

ORPHA:238446 Microduplication syndrome

OMIM: 608636

Prevalence: <1 / 1 000 000

Definition:

The 15q11-q13 microduplication (dup15q11-q13) syndrome is characterized by neurobehavioral disorders, hypotonia, cognitive deficit, language delay and seizures. Prevalence is unknown.

Phenotypic features:

Obligate (100%)	Very frequent (99–80%)	Frequent (79–30%)	Occasional (29–5%)	Very rare (<4-1%)	Excluded (0%)
-	Compulsive behaviors Delayed speech and language development Intellectual disability Hypotonia Global developmental delay Attention deficit hyperactivity disorder	Autism Seizure Apraxia Clinodactyly of the 5th finger	Macrocephaly Epicanthus Mask-like facies Downslanted palpebral fissures Ataxia Joint hypermobility Short stature Finger syndactyly Abnormal cardiovascular system morphology	-	-

ORPHA:3306 Inverted duplication syndrome

OMIM:

Prevalence: 1-9 / 100 000

Definition:

A rare, complex chromosomal duplication/inversion in the region 15q11.2-q13.1 characterized by early central hypotonia, global developmental delay and intellectual deficit, autistic behavior, and seizures.

Phenotypic features:

Obligate (100%)	Very frequent (99–80%)	Frequent (79–30%)	Occasional (29–5%)	Very rare (<4-1%)	Excluded (0%)
-	Autistic behavior Generalized hypotonia Joint hypermobility Drooling	Abnormal repetitive mannerisms Hyperactivity Seizure Severe expressive language delay Echolalia Severe receptive language delay Feeding difficulties Self-biting Neurodevelopmental delay	Posteriorly rotated ears Hypogonadism High palate Brachycephaly Microcephaly Epicanthus Short philtrum Broad nasal tip Strabismus Deeply set eye Downslanted palpebral fissures Synophrys Aggressive behavior Brachydactyly Growth delay Abnormal facial shape Clinodactyly of the 5th finger 2-3 toe syndactyly Abnormality of brain morphology	Cryptorchidism Unilateral renal agenesis Gonadal dysgenesis Precocious puberty Ventricular septal defect Tetralogy of Fallot Talipes equinovarus Hernia	Frontal bossing

Molecular pathway

View on WikiPathways

Gene Information

HGNC	Gene Name	NCBI	Ensembl	UniProt
TUBGCP5	tubulin gamma complex component 5	114791	ENSG00000275835	Q96RT8
CYFIP1	cytoplasmic FMR1 interacting protein 1	23191	ENSG00000273749	Q7L576
NIPA2	NIPA magnesium transporter 2	81614	ENSG00000140157	Q8N8Q9
NIPA1	NIPA magnesium transporter 1	123606	ENSG00000170113	Q7RTP0
GOLGA8S	golgin A8 family member S	653061	ENSG00000261739	H3BPF8
GOLGA6L2	golgin A6 family like 2	283685	ENSG00000174450	Q8N9W4
MKRN3	makorin ring finger protein 3	7681	ENSG00000179455	Q13064
MAGEL2	MAGE family member L2	54551	ENSG00000254585	Q9UJ55
NDN	necdin, MAGE family member	4692	ENSG00000182636	Q99608
NPAP1	nuclear pore associated protein 1	23742	ENSG00000185823	Q9NZP6
SNRPN	small nuclear ribonucleoprotein polypeptide N	6638	ENSG00000128739	P63162
SNURF	SNRPN upstream open reading frame	8926	ENSG00000273173	Q9Y675
UBE3A	ubiquitin protein ligase E3A	7337	ENSG00000114062	Q05086
ATP10A	ATPase phospholipid transporting 10A (putative)	57194	ENSG00000206190	O60312
GABRB3	gamma-aminobutyric acid type A receptor subunit beta3	2562	ENSG00000166206	P28472
GABRA5	gamma-aminobutyric acid type A receptor subunit alpha5	2558	ENSG00000186297	P31644
GABRG3	gamma-aminobutyric acid type A receptor subunit gamma3	2567	ENSG00000182256	Q99928
OCA2	OCA2 melanosomal transmembrane protein	4948	ENSG00000104044	Q04671
HERC2	HECT and RLD domain containing E3 ubiquitin protein ligase 2	8924	ENSG00000128731	O95714

Evidence

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