Fragile Mental Retardation 2
Encyclopedia
Fragile Mental Retardation 2 is a gene (FMR2: synonym AFF2), 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 (FRAXE). FRAXE is one of the most common forms of non-syndromic X-linked mental retardation.
The most common mutation giving rise to this syndrome is a triplet expansion of CCG
in the 5' untranslated region which leads to a silencing of the gene. Mutations within the gene may also cause this phenotype.
and adult brain
.
The normal 5' untranslated region has 10-35 CCG repeats and more frequently 15-20. Pathogenic expansions have typically over 200 repeats and are methylated.
This gene belongs to the AFF family of genes which currently has four members: AFF1
/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.
The other members of this family have been reported to form fusion genes as a consequence of chromosome translocations and are involved in the pathogenesis of myeloid/lymphoid or mixed lineage leukemia
.
A Drosophila
FMR2 orthologue Lilliputian (Lilli) has been identified.
X chromosome
The X chromosome is one of the two sex-determining chromosomes in many animal species, including mammals and is common in both males and females. It is a part of the XY sex-determination system and X0 sex-determination system...
. Mutations in this gene are associated with X linked intellectual disability
X-Linked mental retardation
X-linked mental retardation refers to forms of mental retardation which are specifically associated with X-linked recessive inheritance....
and specifically a syndrome known as fragile X E syndrome (FRAXE). FRAXE is one of the most common forms of non-syndromic X-linked mental retardation.
The most common mutation giving rise to this syndrome is a triplet expansion of CCG
CCG
CCG may refer to:* Canadian Coast Guard* Castor Cracking Group* Centre for Computational Geography* Chemical Computing Group, a pharmaceutical software company based in Montreal, Quebec...
in the 5' untranslated region which leads to a silencing of the gene. Mutations within the gene may also cause this phenotype.
Genomics
This gene is located on the long arm of chromosome X (Xq27.3-Xq28) It has 22 exons spanning at least 500 kb. Alternative splicing may occur and involve exons 2, 3, 5, 7 and 21. The normal encoded protein is 1311 codons in length. It is expressed as an 8.7 kilobase transcript in the placentaPlacenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...
and adult brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
.
The normal 5' untranslated region has 10-35 CCG repeats and more frequently 15-20. Pathogenic expansions have typically over 200 repeats and are methylated.
This gene belongs to the AFF family of genes which currently has four members: AFF1
AFF1
AF4/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.
The other members of this family have been reported to form fusion genes as a consequence of chromosome translocations and are involved in the pathogenesis of myeloid/lymphoid or mixed lineage leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
.
A Drosophila
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...
FMR2 orthologue Lilliputian (Lilli) has been identified.