3q29 microdeletion syndrome
Encyclopedia
3q29 microdeletion syndrome is a rare genetic disorder
resulting from the deletion of a segment of chromosome 3. This syndrome was first described in 2005.
of 3q29 microdeletion syndrome is variable. Clinical features can include mild/moderate mental retardation
with mildly dysmorphic
facial features (long and narrow face, short philtrum
and a high nasal bridge). Of the 6 reported patients, additional features including autism
, ataxia
, chest-wall deformity and long, tapering fingers were found in at least two patients. A review of 14 children with insterstitial deletions of 3q29, found 11 whom had the common recurrent 1.6Mb deletion and displayed mental retardation and microcephaly
.
The variability of phenotype is underscored by the report on a 6 and 9/12 year-old male patient with a de novo chromosome 3q29 microdeletion identified by BAC array comparative genomic hybridization assay (aCGH), with accompanying normal 46,XY high-resolution chromosome analysis. The patient has language-based learning disabilities and behavioral features consistent with diagnoses of autism and attention deficit hyperactivity disorder (ADHD) of the inattentive type. He also displays some other features previously associated with chromosome 3q29 microdeletion such as an elongated face, long fingers, and joint laxity. Most notably the patient, per formal IQ testing, was not found to have frank mental retardation as has been previously reported among patients with chromosome 3q29 terminal deletion, but rather the patient has demonstrated an average full-scale IQ result. This report further expands the phenotypic spectrum to include the possibility of normal intelligence as corroborated by formal, longitudinal psycho-educational testing.
The presence of two homologous
low copy repeats either side of the deletion break-point suggests that nonallelic homologous recombination is the likely mechanism underlying this syndrome.
.
s, in length and encompasses 5 known genes and 17 uncharacterised transcripts. These include transferrin receptor
, Choline-phosphate cytidylyltransferase A
, RNF168
, Serine/threonine-protein kinase
, Nuclear cap-binding protein complex
, Melanotransferrin
, DLG1
and D-beta-hydroxybutyrate dehydrogenase
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
resulting from the deletion of a segment of chromosome 3. This syndrome was first described in 2005.
Clinical description
The clinical phenotypePhenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
of 3q29 microdeletion syndrome is variable. Clinical features can include mild/moderate mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
with mildly dysmorphic
Dysmorphic feature
Dysmorphic feature is a medical term referring to a difference of body structure that is suggestive of a congenital disorder, genetic syndrome, or birth defect. A dysmorphic feature can be a minor and isolated birth defect...
facial features (long and narrow face, short philtrum
Philtrum
The philtrum , is a medial cleft common to many mammals, extending from the nose to the upper lip, and, together with a glandular rhinarium and slit-like nostrils, is believed to constitute the primitive condition for mammals in general...
and a high nasal bridge). Of the 6 reported patients, additional features including autism
Autism
Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
, ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
, chest-wall deformity and long, tapering fingers were found in at least two patients. A review of 14 children with insterstitial deletions of 3q29, found 11 whom had the common recurrent 1.6Mb deletion and displayed mental retardation and microcephaly
Microcephaly
Microcephaly is a neurodevelopmental disorder in which the circumference of the head is more than two standard deviations smaller than average for the person's age and sex. Microcephaly may be congenital or it may develop in the first few years of life...
.
The variability of phenotype is underscored by the report on a 6 and 9/12 year-old male patient with a de novo chromosome 3q29 microdeletion identified by BAC array comparative genomic hybridization assay (aCGH), with accompanying normal 46,XY high-resolution chromosome analysis. The patient has language-based learning disabilities and behavioral features consistent with diagnoses of autism and attention deficit hyperactivity disorder (ADHD) of the inattentive type. He also displays some other features previously associated with chromosome 3q29 microdeletion such as an elongated face, long fingers, and joint laxity. Most notably the patient, per formal IQ testing, was not found to have frank mental retardation as has been previously reported among patients with chromosome 3q29 terminal deletion, but rather the patient has demonstrated an average full-scale IQ result. This report further expands the phenotypic spectrum to include the possibility of normal intelligence as corroborated by formal, longitudinal psycho-educational testing.
The presence of two homologous
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
low copy repeats either side of the deletion break-point suggests that nonallelic homologous recombination is the likely mechanism underlying this syndrome.
Research
Research on the risk for developing schizophrenia in Ashkenazi Jewish and other populations showed that 3q29 microdeletion syndrome leads to a significant higher rate of schizophreniaSchizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
.
Affected genes
The microdeletion, around 1.6 million base pairBase pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
s, in length and encompasses 5 known genes and 17 uncharacterised transcripts. These include transferrin receptor
TFRC
Transferrin receptor protein 1 also known as is a protein that in humans is encoded by the TFRC gene...
, Choline-phosphate cytidylyltransferase A
PCYT1A
Choline-phosphate cytidylyltransferase A is an enzyme that in humans is encoded by the PCYT1A gene.-Further reading:...
, RNF168
RING finger domain
In molecular biology, a RING finger domain is a protein structural domain of zinc finger type which contains a Cys3HisCys4 amino acid motif which binds two zinc cations. This protein domain contains from 40 to 60 amino acids...
, Serine/threonine-protein kinase
PAK2
Serine/threonine-protein kinase PAK 2 is an enzyme that in humans is encoded by the PAK2 gene.-Interactions:PAK2 has been shown to interact with SH3KBP1, CDC42 and Abl gene.-External links:* Info with links in the...
, Nuclear cap-binding protein complex
Nuclear cap-binding protein complex
Nuclear cap-binding protein complex is a RNA-binding protein which binds to the 5' cap of RNA polymerase II. The cap and nuclear cap-binding protein have many function in mRNA biogenesis including splicing, 3'-end formation by stabilizing the interaction of the 3'-end processing machinery, nuclear...
, Melanotransferrin
MFI2
Melanotransferrin is a protein that in humans is encoded by the MFI2 gene. MFI2 has also recently been designated CD228 .-External links:...
, DLG1
DLG1
Disks large homolog 1 , also known as synapse-associated protein 97 or SAP97, is a protein that in humans is encoded by the SAP97 gene....
and D-beta-hydroxybutyrate dehydrogenase
BDH1
D-beta-hydroxybutyrate dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the BDH1 gene.-Further reading:...