PYCR1

Cutis laxa

PYCR1 gene variants (also known as mutations) have been identified in people with cutis laxa. Variants in this gene cause a form of the disorder called autosomal recessive cutis laxa type 2B (ARCL2B), which is characterized by loose, wrinkled, sagging skin that is often described as parchment-like; prominant veins; distinctive facial features; and  larger than normal spaces (fontanelles) between the skull bones that close later than usual. Some affected individuals also have delayed development, intellectual disability, or bone abnormalities. Some researchers suggest all cases of cutis laxa caused by PYCR1 gene variants are considered ARCL2B, while others consider the most severe cases to be another form of the disorder called autosomal recessive cutis laxa type 3B (ARCL3B, which is also known as de Barsy syndrome).

PYCR1 gene variants prevent the production of functional PYCR1 protein. A shortage of this protein impairs mitochondrial function, which leads to increased cell death, particularly when cells are under stress. Excessive death of skin and nerve cells is thought to underlie the characteristic features of ARCL2B and ARCL3B. Although the PYCR1 protein is involved in the formation of proline, levels of this amino acid are normal in individuals with ARCL2B and ARCL3B. It is unclear if disruption of proline formation plays a role in the development of cutis laxa.