X-Linked mental retardation
Encyclopedia
X-linked mental retardation (also known as X-linked intellectual disability) refers to forms of mental retardation
which are specifically associated with X-linked recessive inheritance.
Unlike many other types of mental retardation, the genetics of these conditions are relatively well understood.
As with most X-linked disorders, males are more heavily affected than females. Females with one affected X and one normal X tend to have milder symptoms.
This form of intellectual disability accounts for ~16% of all cases in males. It has been estimated there are ~200 genes involved in this syndrome; of these ~100 have been identified.
, MASA syndrome
, and X-linked alpha thalassemia mental retardation syndrome.
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...
which are specifically associated with X-linked recessive inheritance.
Unlike many other types of mental retardation, the genetics of these conditions are relatively well understood.
As with most X-linked disorders, males are more heavily affected than females. Females with one affected X and one normal X tend to have milder symptoms.
This form of intellectual disability accounts for ~16% of all cases in males. It has been estimated there are ~200 genes involved in this syndrome; of these ~100 have been identified.
Syndromes
Several X-linked syndromes include retardation as part of the presentation. These include Coffin-Lowry syndromeCoffin-Lowry syndrome
Coffin-Lowry syndrome is a genetic disorder that is X-linked dominant and which causes severe mental problems sometimes associated with abnormalities of growth, cardiac abnormalities, kyphoscoliosis, as well as auditory and visual abnormalities.-History:...
, MASA syndrome
MASA syndrome
MASA syndrome, also called CRASH syndrome and Gareis-Mason syndrome, is a rare X-linked recessive neurological disorder.The acronym "MASA" describes the four major symptoms - Mental retardation, Aphasia, Shuffling gait, and Adducted thumbs. The disorder has been associated with mutations in the...
, and X-linked alpha thalassemia mental retardation syndrome.
List of genes
Following is a list of genes located on the X chromosome and linked to mental retardation. There are also several loci that have not been associated with a specific gene.- IQSEC2IQSEC2IQ motif and Sec7 domain 2 is a protein that in humans is encoded by the IQSEC2 gene.- Function :The IQSEC2 gene encodes a guanine nucleotide exchange factor for the ARF family of GTP-binding proteins ....
: encodes an exchange factor for the Arf family of small GTP binding proteins, involved in the formation of secretory vesicles. - TM4SF2: is a member of the 4 transmembrane domains family of proteins (tetraspanins, see TSPAN7TSPAN7Tetraspanin-7 is a protein that in humans is encoded by the TSPAN7 gene.-Further reading:...
). This gene is also associated with neuropsychiatric diseases such as Huntington's chorea. - AP1S2AP1S2AP-1 complex subunit sigma-2 is a protein that in humans is encoded by the AP1S2 gene.-Further reading:...
: AP-1 complex subunit sigma-2. Adaptor protein complex 1 is found on the cytoplasmic face of vesicles located at the Golgi complex, where it mediates both the recruitment of clathrin to the membrane and the recognition of sorting signals within the cytosolic tails of transmembrane receptors. - ACSL4ACSL4Long-chain-fatty-acid—CoA ligase 4 is an enzyme that in humans is encoded by the ACSL4 gene.-Further reading:...
: Long-chain-fatty-acid—CoA ligase 4 is an enzymeEnzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
of the long-chain fatty-acid-coenzyme A ligaseLigaseIn biochemistry, ligase is an enzyme that can catalyse the joining of two large molecules by forming a new chemical bond, usually with accompanying hydrolysis of a small chemical group dependent to one of the larger molecules...
family. It converts free long-chain fatty acids into fatty acylAcylAn acyl group is a functional group derived by the removal of one or more hydroxyl groups from an oxoacid, including inorganic acids.In organic chemistry, the acyl group is usually derived from a carboxylic acid . Therefore, it has the formula RCO-, where R represents an alkyl group that is...
-CoACOACOA can refer to:*Codename Amscray*Cash on Arrival*Cause of action*CedarOpenAccounts*Center of Attention*Certificate of Appealability*Certificate of Approval for marriage or civil partnership in the United Kingdom*Certificate of Authenticity...
esterEsterEsters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
s, and thereby play a key role in lipidLipidLipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
biosynthesisBiosynthesisBiosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
and fatty acid degradation. This isozyme preferentially utilizes arachidonate as substrateSubstrate (biochemistry)In biochemistry, a substrate is a molecule upon which an enzyme acts. Enzymes catalyze chemical reactions involving the substrate. In the case of a single substrate, the substrate binds with the enzyme active site, and an enzyme-substrate complex is formed. The substrate is transformed into one or...
. - ZNF41ZNF41Zinc finger protein 41 is a protein that in humans is encoded by the ZNF41 gene....
: Zinc finger protein 41 is a likely zinc finger family transcription factor. - DLG3DLG3Disks large homolog 3 also known as neuroendocrine-DLG or synapse-associated protein 102 is a protein that in humans is encoded by the DLG3 gene...
: Disks large homolog 3, also named neuroendocrine-DLG or synapse-associated protein 102 (SAP-102). DLG3 is a member of the membrane-associated guanylate kinaseMembrane-associated guanylate kinaseThe membrane-associated guanylate kinases are a superfamily of proteins. The MAGUKs are defined by their inclusion of PDZ, SH3 and GUK domains, although many of them also contain regions homologous of CaMKII, WW and L27 domains...
(MAGUK) superfamily. - FTSJ1FTSJ1Putative ribosomal RNA methyltransferase 1 is an enzyme that in humans is encoded by the FTSJ1 gene.-Further reading:...
: Putative ribosomal RNA methyltransferase 1 is a member of the S-adenosylmethionine-binding protein family. This nucleolar protein may be involved in the processing and modification of rRNA. - GDI1GDI1Rab GDP dissociation inhibitor alpha is a protein that in humans is encoded by the GDI1 gene.Rab GTPases cycles between the cytosolic compartment, where it is bound to a protein called GDI , and the membrane, where it interacts with a receptor, a nucleotide exchange factor, a GAP and probably...
: RabGDI alpha makes a complex with geranylgeranylated small GTP-binding proteins of the Rab family and keeps them in the cytosol. - MECP2MECP2MECP2 is a gene that provides instructions for making its protein product, MECP2, also referred to as MeCP2. MECP2 appears to be essential for the normal function of nerve cells. The protein seems to be particularly important for mature nerve cells, where it is present in high levels...
: methyl CpG binding protein 2 is a transcription regulator, which represses transcription from methylated gene promoters. It appears to be essential for the normal function of nerve cells. In contrast to other MBD family members, MECP2 is X-linked and subject to X inactivation. MECP2 gene mutations are the cause of most cases of Rett syndromeRett syndromeRett syndrome is a neurodevelopmental disorder of the grey matter of the brain that almost exclusively affects females. The clinical features include small hands and feet and a deceleration of the rate of head growth . Repetitive hand movements, such as wringing and/or repeatedly putting hands into...
, a progressive neurologic developmental disorder and one of the most common causes of mental retardation in woman. - ARXAristaless related homeoboxAristaless related homeobox, also known as ARX is a protein associated with mental retardation and lissencephaly....
: Aristaless related homeobox, is a protein associated with mental retardationMental retardationMental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
and lissencephalyLissencephalyLissencephaly, which literally means smooth brain, is a rare brain formation disorder caused by defective neuronal migration during the 12th to 24th weeks of gestation, resulting in a lack of development of brain folds and grooves . It is a form of cephalic disorder...
. This gene is a homeobox-containing gene expressed during development. The expressed protein contains two conserved domains, a C-peptide (or aristaless domain) and the prd-like class homeobox domain. It is a member of the group-II aristaless-related protein family whose members are expressed primarily in the central and/or peripheral nervous system. This gene is involved in CNS and pancreas development. Mutations in this gene cause X-linked mental retardation and epilepsy. - JARID1CJARID1CLysine-specific demethylase 5C is an enzyme that in humans is encoded by the KDM5C gene....
: Lysine-specific demethylase 5C is an enzymeEnzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
that in humans is encoded by the KDM5C geneGeneA gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
a member of the SMCY homolog family and encodes a protein with one ARID domainARID domainIn molecular biology, the ARID domain ) is a protein domain that binds to DNA. ARID domain-containing proteins are found in fungi and invertebrate and vertebrate metazoans. ARID-encoding genes are involved in a variety of biological processes including embryonic development, cell lineage gene...
, one JmjC domain, one JmjN domain and two PHD-type zinc fingers. The DNA-binding motifs suggest this protein is involved in the regulation of transcription and chromatin remodeling. - PHF8PHF8PHD finger protein 8 is a protein that in humans is encoded by the PHF8 gene.- Function :PHF8 belongs to the family of ferrous iron and 2-oxoglutarate dependent oxygenases, and is active as a histone lysine demethylase with selectivity for the di-and monomethyl states.- Clinical significance...
: PHD finger protein 8 belongs to the family of ferrous iron and 2-oxoglutarate dependent oxygenases, and is an histoneHistoneIn biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...
lysine demethylase with selectivity for the di-and monomethyl states. - FMR2Fragile Mental Retardation 2Fragile Mental Retardation 2 is a gene , located on the human X chromosome. Mutations in this gene are associated with X linked intellectual disability and specifically a syndrome known as fragile X E syndrome...
: Fragile Mental Retardation 2 (FMR2: synonym AFF2), the protein belongs to the AFF family which currently has four members: AFF1AFF1AF4/FMR2 family member 1 is a protein that in humans is encoded by the AFF1 gene.-Further reading:...
/AF4, AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31. All AFF proteins are localized in the nucleus and have a role as transcriptional activators with a positive action on RNA elongation. AFF2/FMR2, AFF3/LAF4 and AFF4/AF5q31 localize in nuclear speckles (subnuclear structures considered to be storage/modification sites of pre-mRNA splicing factors) and are able to bind RNA with a high apparent affinity for the G-quadruplex structure. They appear to modulate alternative splicing via the interaction with the G-quadruplex RNA-forming structure.