Chromodomain-helicase-DNA-binding protein 7 is an ATP-dependent 'chromatin' or 'nucleosome' remodeling factor [5] that in humans is encoded by the CHD7 gene. [6] [7]
CHD7 is an ATP-dependent chromatin remodeler homologous to the Drosophila trithorax-group protein Kismet. [8] Mutations in CHD7 are associated with CHARGE syndrome. [9] This protein belongs to a larger group of ATP-dependent chromatin remodeling complexes, the CHD subfamily.
Mutations in this gene have been associated with the CHARGE syndrome.
CHARGE syndrome is a rare syndrome caused by a genetic disorder. First described in 1979, the acronym "CHARGE" came into use for newborn children with the congenital features of coloboma of the eye, heart defects, atresia of the nasal choanae, restricted growth or development, genital or urinary abnormalities, and ear abnormalities and deafness. These features are no longer used in making a diagnosis of CHARGE syndrome, but the name remains. About two thirds of cases are due to a CHD7 mutation. CHARGE syndrome occurs only in 0.1–1.2 per 10,000 live births; as of 2009, it was the leading cause of congenital deafblindness in the US.
T-box transcription factor TBX1 also known as T-box protein 1 and testis-specific T-box protein is a protein that in humans is encoded by the TBX1 gene. Genes in the T-box family are transcription factors that play important roles in the formation of tissues and organs during embryonic development. To carry out these roles, proteins made by this gene family bind to specific areas of DNA called T-box binding element (TBE) to control the expression of target genes.
22q13 deletion syndrome, known as Phelan–McDermid syndrome (PMS), is a genetic disorder caused by deletions or rearrangements on the q terminal end of chromosome 22. Any abnormal genetic variation in the q13 region that presents with significant manifestations (phenotype) typical of a terminal deletion may be diagnosed as 22q13 deletion syndrome. There is disagreement among researchers as to the exact definition of 22q13 deletion syndrome. The Developmental Synaptopathies Consortium defines PMS as being caused by SHANK3 mutations, a definition that appears to exclude terminal deletions. The requirement to include SHANK3 in the definition is supported by many but not by those who first described 22q13 deletion syndrome.
Twist-related protein 1 (TWIST1) also known as class A basic helix–loop–helix protein 38 (bHLHa38) is a basic helix-loop-helix transcription factor that in humans is encoded by the TWIST1 gene.
The autoimmune regulator (AIRE) is a protein that in humans is encoded by the AIRE gene. It is a 13kbp gene on chromosome 21q22.3 that encodes 545 amino acids. AIRE is a transcription factor expressed in the medulla of the thymus. It is part of the mechanism which eliminates self-reactive T cells that would cause autoimmune disease. It exposes T cells to normal, healthy proteins from all parts of the body, and T cells that react to those proteins are destroyed.
Structural maintenance of chromosomes protein 1A (SMC1A) is a protein that in humans is encoded by the SMC1A gene. SMC1A is a subunit of the cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. In somatic cells, cohesin is formed of SMC1A, SMC3, RAD21 and either SA1 or SA2 whereas in meiosis, cohesin is formed of SMC3, SMC1B, REC8 and SA3.
Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out by 1) covalent histone modifications by specific enzymes, e.g., histone acetyltransferases (HATs), deacetylases, methyltransferases, and kinases, and 2) ATP-dependent chromatin remodeling complexes which either move, eject or restructure nucleosomes. Besides actively regulating gene expression, dynamic remodeling of chromatin imparts an epigenetic regulatory role in several key biological processes, egg cells DNA replication and repair; apoptosis; chromosome segregation as well as development and pluripotency. Aberrations in chromatin remodeling proteins are found to be associated with human diseases, including cancer. Targeting chromatin remodeling pathways is currently evolving as a major therapeutic strategy in the treatment of several cancers.
Tumor protein p63, typically referred to as p63, also known as transformation-related protein 63 is a protein that in humans is encoded by the TP63 gene.
Endothelin receptor type B, (ET-B) is a protein that in humans is encoded by the EDNRB gene.
Transcriptional regulator ATRX also known as ATP-dependent helicase ATRX, X-linked helicase II, or X-linked nuclear protein (XNP) is a protein that in humans is encoded by the ATRX gene.
DNA excision repair protein ERCC-6 is a protein that in humans is encoded by the ERCC6 gene. The ERCC6 gene is located on the long arm of chromosome 10 at position 11.23.
Forkhead box protein L2 is a protein that in humans is encoded by the FOXL2 gene.
Chromodomain-helicase-DNA-binding protein 3 is an enzyme that in humans is encoded by the CHD3 gene.
Transcription factor SOX-18 is a protein that in humans is encoded by the SOX18 gene.
Cohesin subunit SA-2 (SA2) is a protein that in humans is encoded by the STAG2 gene. SA2 is a subunit of the Cohesin complex which mediates sister chromatid cohesion, homologous recombination and DNA looping. In somatic cells cohesin is formed of SMC3, SMC1, RAD21 and either SA1 or SA2 whereas in meiosis, cohesin is formed of SMC3, SMC1B, REC8 and SA3.
PHD finger protein 6 is a protein that in humans is encoded by the PHF6 gene.
Chromodomain-helicase-DNA-binding protein 2 is an enzyme that in humans is encoded by the CHD2 gene.
TOX high mobility group box family member 3, also known as TOX3, is a human gene.
9q34 deletion syndrome is a rare genetic disorder. Terminal deletions of chromosome 9q34 have been associated with childhood hypotonia, a distinctive facial appearance and developmental disability. The facial features typically described include arched eyebrows, small head circumference, midface hypoplasia, prominent jaw and a pouting lower lip. Individuals with this disease may often have speech impediments, such as speech delays. Other characteristics of this disease include: epilepsy, congenital and urogenital defects, microcephaly, corpulence, and psychiatric disorders. From analysis of chromosomal breakpoints, as well as gene sequencing in suggestive cases, Kleefstra and colleagues identified EHMT1 as the causative gene. This gene is responsible for producing the protein histone methyltransferase which functions to alter histones. Ultimately, histone methyltransferases are important in deactivating certain genes, needed for proper growth and development. Moreover, a frameshift, missense, or nonsense error in the coding sequence of EHMT1 can result in this condition in an individual.
Xp11.2 duplication is a genomic variation marked by the duplication of an X chromosome region on the short arm p at position 11.2, defined by standard karyotyping (G-banding). This gene-rich, rearrangement prone region can be further divided into three loci - Xp11.21, Xp11.22 and Xp11.23. The duplication could involve any combination of these three loci. While the length of the duplication can vary from 0.5Mb to 55 Mb, most duplications measure about 4.5Mb and typically occur in the region of 11.22-11.23. Most affected females show preferential activation of the duplicated X chromosome. Features of affected individuals vary significantly, even among members of the same family. The Xp11.2 duplication can be 'silent' - presenting no obvious symptoms in carriers - which is known from the asymptomatic parents of affected children carrying the duplication. The common symptoms include intellectual disabilities, speech delay and learning difficulties, while in rare cases, children have seizures and a recognizable brain wave pattern when assessed by EEG (electroencephalography).
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