Wolf-Hirschhorn syndrome candidate 1 is involved in the cellular response to DNA damage.

[wolf-hirschhorn syndrome]

Wolf-Hirschhorn syndrome (WHS ) is a malformation syndrome associated with growth retardation , mental retardation , and immunodeficiency resulting from a hemizygous deletion of the short arm of chromosome 4 , called the WHS critical region (WHSC ). The WHSC 1 gene is located in this region , and its loss is believed to be responsible for a number of WHS characteristics . We identified WHSC 1 in a genetic screen for genes involved in responding to replication stress , linking Wolf-Hirschhorn syndrome to the DNA damage response (DDR ). Here , we report that the WHSC 1 protein is a member of the DDR pathway . WHSC 1 localizes to sites of DNA damage and replication stress and is required for resistance to many DNA-damaging and replication stress-inducing agents . Through its SET domain , WHSC 1 regulates the methylation status of the histone H 4 K 20 residue and is required for the recruitment of 53 BP 1 to sites of DNA damage . We propose that Wolf-Hirschhorn syndrome results from a defect in the DDR .

Diseases
Validation

Diseases presenting "mental retardation" symptom

achondroplasia

alexander disease

alpha-thalassemia

aniridia

aromatase deficiency

canavan disease

classical phenylketonuria

coats disease

cohen syndrome

cowden syndrome

cystinuria

dentin dysplasia

familial hypocalciuric hypercalcemia

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

kabuki syndrome

kallmann syndrome

lamellar ichthyosis

lymphangioleiomyomatosis

monosomy 21

phenylketonuria

primary hyperoxaluria type 1

proteus syndrome

pyruvate dehydrogenase deficiency

sneddon syndrome

triple a syndrome

wolf-hirschhorn syndrome

zellweger syndrome

This symptom has already been validated