PHD finger protein 8 is a protein that in humans is encoded by the PHF8 gene. [5]
PHD finger protein 8 is a protein that in humans is encoded by the PHF8 gene. [5]
PHF8 belongs to the family of ferrous iron and alpha-ketoglutarate-dependent hydroxylases superfamily., [6] and is active as a histone lysine demethylase with selectivity for the di-and monomethyl states. [7] PHF8 induces an EMT (epithelial to mesenchymal transition)-like process by upregulating key EMT transcription factors SNAI1 and ZEB1.
PHF8 was found to be expressional increased during endothelial differentiation and significantly decreased during cardial differentiation of murine embryonic stem cells. [8]
Mutations in PHF8 cause Siderius type X-linked intellectual disability (XLMR) (OMIM : 300263). [9] [10] [11] In addition to moderate intellectual disability, features of the Siderius-Hamel syndrome include facial dysmorphism, cleft lip and/or cleft palate, and in some cases microcephaly. [12] [13] [14] A chromosomal microdeletion on Xp11.22 encompassing all of the PHF8 and FAM120C genes and a part of the WNK3 gene was reported in two brothers with autism spectrum disorder in addition to Siderius-type XLMR and cleft lip and palate. [15]
This catalytic activity is disrupted by clinically known mutations to PHF8, which were found to cluster in its catalytic JmjC domain. The F279S mutation of PHF8, found in 2 Finnish brothers with mild intellectual disability, facial dysmorphism and cleft lip/palate, [14] was found to additionally prevent nuclear localisation of PHF8 overexpressed in human cells. [7]
The catalytic activity of PHF8 depends on molecular oxygen, [7] a fact considered important with respect to reports on increased incidence of cleft lip/palate in mice that have been exposed to hypoxia during pregnancy. [16] In humans, fetal cleft lip and other congenital abnormalities have also been linked to maternal hypoxia, as caused by e.g. maternal smoking, [17] heavy maternal alcohol use, or maternal hypertension treatment. [18]
A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate contains an opening into the nose. The term orofacial cleft refers to either condition or to both occurring together. These disorders can result in feeding problems, speech problems, hearing problems, and frequent ear infections. Less than half the time the condition is associated with other disorders.
MASA syndrome is a rare X-linked recessive neurological disorder on the L1 disorder spectrum belonging in the group of hereditary spastic paraplegias a paraplegia known to increase stiffness spasticity in the lower limbs. This syndrome also has two other names, CRASH syndrome and Gareis-Mason syndrome.
Abruzzo–Erickson syndrome is an extremely rare disorder characterized by deafness, protruding ears, coloboma, a cleft palate or palatal rugosity, radial synostosis, and short stature. It was first characterized by Abruzzo and Erickson in 1977 as a CHARGE like syndrome as variably expressed among a family of two brothers, their mother, and their maternal uncle. Members of this family exhibited many of the CHARGE symptoms, but notably did not have choanal atresia and the brothers experienced typical genital development. Due to the recent discovery of this disorder, its etiology is not fully known but it is understood that it arises from mutations on the TBX22 gene on the X-chromosome. The disorder is inherited in an X-linked recessive manner. There is currently no known cure but its symptoms can be treated.
Hay–Wells syndrome is one of at least 150 known types of ectodermal dysplasia. These disorders affect tissues that arise from the ectodermal germ layer, such as skin, hair, and nails.
Rosselli–Gulienetti syndrome, also known as Zlotogora–Ogur syndrome and Bowen–Armstrong syndrome, is a type of congenital ectodermal dysplasia syndrome. The syndrome is relatively rare and has only been described in a few cases.
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.
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.
Transcription factor SOX-3 is a protein that in humans is encoded by the SOX3 gene. This gene encodes a member of the SOX family of transcription factors involved in the regulation of embryonic brain development and in determination of cell fate. The encoded protein acts as a transcriptional activator.
Lysine-specific demethylase 5C is an enzyme that in humans is encoded by the KDM5C gene. KDM5C belongs to the alpha-ketoglutarate-dependent hydroxylase superfamily.
Transcription factor AP-2 alpha, also known as TFAP2A, is a protein that in humans is encoded by the TFAP2A gene.
Putative ribosomal RNA methyltransferase 1 is an enzyme that in humans is encoded by the FTSJ1 gene.
T-box transcription factor TBX22 is a protein that in humans is encoded by the TBX22 gene.
X-linked intellectual disability refers to medical disorders associated with X-linked recessive inheritance that result in intellectual disability.
Lujan–Fryns syndrome (LFS) is an X-linked genetic disorder that causes mild to moderate intellectual disability and features described as Marfanoid habitus, referring to a group of physical characteristics similar to those found in Marfan syndrome. These features include a tall, thin stature and long, slender limbs. LFS is also associated with psychopathology and behavioral abnormalities, and it exhibits a number of malformations affecting the brain and heart. The disorder is inherited in an X-linked dominant manner, and is attributed to a missense mutation in the MED12 gene. There is currently no treatment or therapy for the underlying MED12 malfunction, and the exact cause of the disorder remains unclear.
Special AT-rich sequence-binding protein 2 (SATB2) also known as DNA-binding protein SATB2 is a protein that in humans is encoded by the SATB2 gene. SATB2 is a DNA-binding protein that specifically binds nuclear matrix attachment regions and is involved in transcriptional regulation and chromatin remodeling. SATB2 shows a restricted mode of expression and is expressed in certain cell nuclei. The SATB2 protein is mainly expressed in the epithelial cells of the colon and rectum, followed by the nuclei of neurons in the brain.
Malpuech facial clefting syndrome, also called Malpuech syndrome or Gypsy type facial clefting syndrome, is a rare congenital syndrome. It is characterized by facial clefting, a caudal appendage, growth deficiency, intellectual and developmental disability, and abnormalities of the renal system (kidneys) and the male genitalia. Abnormalities of the heart, and other skeletal malformations may also be present. The syndrome was initially described by Georges Malpuech and associates in 1983. It is thought to be genetically related to Juberg-Hayward syndrome. Malpuech syndrome has also been considered as part of a spectrum of congenital genetic disorders associated with similar facial, urogenital and skeletal anomalies. Termed "3MC syndrome", this proposed spectrum includes Malpuech, Michels and Mingarelli-Carnevale (OSA) syndromes. Mutations in the COLLEC11 and MASP1 genes are believed to be a cause of these syndromes. The incidence of Malpuech syndrome is unknown. The pattern of inheritance is autosomal recessive, which means a defective (mutated) gene associated with the syndrome is located on an autosome, and the syndrome occurs when two copies of this defective gene are inherited.
ARHGAP29 is a gene located on chromosome 1p22 that encodes Rho GTPase activating protein (GAP) 29, a protein that mediates the cyclical regulation of small GTP binding proteins such as RhoA.
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).
Stocco dos Santos syndrome is an extremely rare multi-systemic genetic disorder which is present from birth. It is characterized by heart, skeletal, muscular abnormalities with accompanying intellectual disabilities.
Holoprosencephaly-ectrodactyly-cleft lip/palate syndrome, also simply known as Hartsfield syndrome, is a rare genetic disorder characterized by the presence of variable holoprosencephaly, ectrodactyly, cleft lip and palate, alongside generalized ectodermal abnormalities. Additional findings include endocrine anomalies and developmental delays.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
