Wiedemann-Rautenstrauch syndrome - POLR3A gene
The Wiedemann-Rautenstrauch syndrome, also known as neonatal progeroid syndrome or congenital pseudo-hydrocephalic progeroid syndrome, is a type of genetic disorder characterized by the rapid and dramatic onset of aging earlier than expected.
The signs and symptoms of this process generally include lack of growth and weight gain; distinctive facial features that give the appearance of old age, such as a large head, a triangular face with a prominent forehead and a pointed chin, small mouth with a thin upper lip, low implant ears, abnormal lower eyelids, half retraction of the face; sparse hair; lipodystrophy, particularly in the face, arms and legs; thin and translucent skin; and in some cases, development of contractures. Other signs may include fontanelles that may remain open throughout life; dental problems such as premature tooth fall after birth or hypodontia; and movement problems, such as ataxia and tremors.
The life expectancy of individuals with Wiedemann-Rautenstrauch syndrome is variable. Some affected individuals do not survive childhood, while others live until early adulthood.
This process is due to mutations in the POLR3A (RNA polymerase III subunit A) gene, located on the long arm of chromosome 10 (10q22.3), which encodes a subunit of the RNA polymerase III enzyme. This enzyme participates in the synthesis of various forms of RNA, including rRNA (ribosomal RNA) and tRNA (transfer RNA). The rRNA and tRNA molecules assemble amino acids into functional proteins, this process being essential for normal functioning and cell survival.
Mutations in the POLR3A gene result in the synthesis of subunits of abnormal proteins that are thought to affect the function of RNA polymerase III. Abnormal subunits can prevent the binding of the RNA polymerase III enzyme or result in an RNA polymerase III with decreased ability to synthesize RNA. Although the reduced function of the RNA polymerase III molecule probably affects the development and function of many parts of the body, it is unknown how mutations in the POLR3A gene give rise to the specific signs and symptoms of this syndrome.
This disease is inherited with an autosomal recessive pattern, that is, both copies of the gene in each cell must have mutations for the alteration to be expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually do not show signs and symptoms of the disease.
Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with the Wiedemann-Rautenstrauch syndrome, by means of the complete PCR amplification of the exons of the POLR3A gene, and their subsequent sequencing.
Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leucocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).