A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome

@article{Risheg2007ARM,
  title={A recurrent mutation in MED12 leading to R961W causes Opitz-Kaveggia syndrome},
  author={Hiba Risheg and John M Graham and Robin Dawn Clark and Roger Curtis Rogers and John M Opitz and John B. Moeschler and Andreas Peiffer and Melanie M. May and Sumy M Joseph and Julie R. Jones and Roger E. Stevenson and Charles E. Schwartz and Michael J. Friez},
  journal={Nature Genetics},
  year={2007},
  volume={39},
  pages={451-453}
}
Opitz-Kaveggia syndrome (also known as FG syndrome) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. We report here that the original family for whom the condition is named and five other families have a recurrent mutation (2881C>T, leading to R961W) in MED12 (also called TRAP230 or HOPA), a gene located at Xq13 that functions as a thyroid receptor–associated protein in the Mediator complex. 

A novel mutation in MED 12 causes FG syndrome ( Opitz – Kaveggia syndrome )

TLDR
This is the first demonstration that other mutations in this gene can also lead to Opitz–Kaveggia syndrome, and a new family with three affected cousins is identified, in which a novel MED12 mutation (p.G958E) is identified.

A novel mutation in MED12 causes FG syndrome (Opitz–Kaveggia syndrome)

TLDR
A novel mutation in MED12 causes FG syndrome (Opitz–Kaveggia syndrome) and further studies are needed to establish a causative mechanism.

A novel MED12 mutation associated with non-specific X-linked intellectual disability

TLDR
A novel non-synonymous single-nucleotide variant is identified in a male patient with non-specific X-linked intellectual disability (XLID) and the existence of similar reports suggest a relationship between MED12 variants and XLID.

Nonsyndromic X-linked intellectual deficiency in three brothers with a novel MED12 missense mutation [c.5922G>T (p.Glu1974His)]

TLDR
A novel mutation segregating with XLID phenotype is reported, which could be in favor of genotype–phenotype correlations.

gene MED12 missense mutation (p.N1007S) in the The original Lujan syndrome family has a novel

A novel missense mutation in the mediator of RNA polymerase II transcription subunit 12 ( MED12 ) gene has been found in the original family with Lujan syndrome and in a second family (K9359) that

MED13L loss‐of‐function variants in two patients with syndromic Pierre Robin sequence

TLDR
The findings suggest that MED13L–related disorders are a possible differential diagnosis for syndromic PRS, and the finding of an essential splice site mutation in mediator complex subunit 13 like (MED13L) in one patient prompted the investigation of copy number variants in MED13 L in the other, leading to the identification of an intragenic deletion.

Mutations in MED12 cause X-linked Ohdo syndrome.

Two male sibs with severe micrognathia and a missense variant in MED12.

The original Lujan syndrome family has a novel missense mutation (p.N1007S) in the MED12 gene

TLDR
It seems that these two X-linked mental retardation syndromes are allelic, with mutations in the MED12 gene.

Clinical and neurocognitive characterization of a family with a novel MED12 gene frameshift mutation

TLDR
The severe degree of ID in male patients, as well as variable cognitive impairment in heterozygous females, suggests that the duplication observed in the present family may have a more severe effect on MED12 function than missense mutations.
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References

SHOWING 1-10 OF 16 REFERENCES

Association studies of the HOPA dodecamer duplication variant in different subtypes of autism.

TLDR
The frequency of this 12 bp duplication variant of the HOPA gene has major relevance to the susceptibility to different subtypes of autism at least in this German patient sample, and a new splice variant that utilizes an additional 9 bp of the 3' intron subsequent to exon 39 is identified.

Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene.

TLDR
Although clinical signs of thyroid dysfunction are usually absent in affected males, the disturbances in blood levels of thyroid hormones suggest the possibility of systematic detection through screening of high-risk populations.

X‐linked mental retardation: further lumping, splitting and emerging phenotypes

X‐linked mental retardation (XLMR) is a very heterogeneous condition, subdivided in two categories mainly based on clinical features: syndromic XLMR (MRXS) and non‐syndromic XLMR (MRX). Although it

Association of an X-chromosome dodecamer insertional variant allele with mental retardation

TLDR
The presence of this 12-bp variant confers significant susceptibility for mental retardation, and the findings suggested an increased incidence of histories of hypothyroidism and treatment with antidepressants.

The FG syndrome: Report of a large Italian series

TLDR
Experience with the series of patients suggests that the FG syndrome may be common, and should be routinely considered in the evaluation of children and adolescents with DD/MR, and the syndrome appears to be characterized by ADHD.

A gene for FG syndrome maps in the Xq12-q21.31 region.

TLDR
The results of a new linkage analysis performed on 10 families including that studied by Zhu et al.

Evidence that a dodecamer duplication in the gene HOPA in Xq13 is not associated with mental retardation.

TLDR
Results of four studies in four different populations do not corroborate the findings of the previous study, and indicate that the HOPA dodecamer duplication does not convey an increased susceptibility to mental retardation.

Studies of malformation syndromes of man XXXIII: The FG syndrome. An X-linked recessive syndrome of multiple congenital anomalies and mental retardation

Three brothers and two of their male first cousins were affected with a previously apparently undefined multiple congenital anomaly, mental retardation syndrome which was designated the FG syndrome

The zebrafish kohtalo/trap230 gene is required for the development of the brain, neural crest, and pronephric kidney.

TLDR
Results suggest that critical targets of TRAP230 function may include proteins important for cell mobility, cell sorting, and tissue assembly.

Systematic mapping of genetic interactions in Caenorhabditis elegans identifies common modifiers of diverse signaling pathways

TLDR
It is proposed that these genes function as general buffers of genetic variation and that these hub genes may act as modifier genes in multiple, mechanistically unrelated genetic diseases in humans.