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About SRD5A3

SRD5A3-CDG Summary

SRD5A3-CDG is a rare, non X-linked congenital disorder of glycosylation due to steroid 5 alpha reductase type 3 deficiency characterized by a highly variable phenotype typically presenting with severe visual impairment, variable ocular anomalies (such as optic nerve hypoplasia/atrophy, iris and optic nerve coloboma, congenital cataract, glaucoma), intellectual disability, cerebellar abnormalities, nystagmus, hypotonia, ataxia, and/or ichthyosiform skin lesions. Other reported manifestations include retinitis pigmentosa, kyphosis, congenital heart defects, hypertrichosis and abnormal coagulation.  For more details click here 

W19X is a common SRD5A3-CDG mutation. This mutation results in a truncated, non-functional SRD5A3 protein in patients, as illustrated in the figure below. 

Lay overview. Steroid 5a-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG, also known as CDG1q) is an ultra-rare genetic disorder caused by mutations in the SRD5A3 gene that results in developmental delays and problems with vision. SRD5A3-CDG disrupts normal patterns glycosylation, in which glycan sugar groups are added to proteins to change their functions and location in cells. SRD5A3 gene mutations disrupt the function of the important enzyme polyprenol reductase. SRD5A3-CDG is a potential candidate for the development of new therapies ranging from specialized dietary supplementation to advanced medicine like gene therapy.

Gene function. Steroid 5a-reductase type 3 (SRD5A3) plays a critical role in the early steps of protein N-linked glycosylation by being required for the conversion of polyprenol into dolichol. Dolichols are required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-glycosylation. The SRD5A3 protein is a polyprenol reductase enzyme that promotes the reduction of the alpha-isoprene unit of polyprenols into dolichols in a NADP-dependent mechanism. SRD5A3 is also able to convert testosterone (T) into 5-alpha-dihydrotestosterone (DHT).

SRD5A3-CDG is a rare, non X-linked congenital disorder of glycosylation due to steroid 5 alpha reductase type 3 deficiency characterized by a highly variable phenotype typically presenting with severe visual impairment, variable ocular anomalies (such as optic nerve hypoplasia/atrophy, iris and optic nerve coloboma, congenital cataract, glaucoma), intellectual disability, cerebellar abnormalities, nystagmus, hypotonia, ataxia, and/or ichthyosiform skin lesions. Other reported manifestations include retinitis pigmentosa, kyphosis, congenital heart defects, hypertrichosis and abnormal coagulation. FOR MORE DETAILS CLICK HERE 

The protein encoded by this gene belongs to the steroid 5-alpha reductase family, and polyprenol reductase subfamily. It is involved in the production of androgen 5-alpha-dihydrotestosterone (DHT) from testosterone, and maintenance of the androgen-androgen receptor activation pathway. This protein is also necessary for the conversion of polyprenol into dolichol, which is required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-linked glycosylation of proteins. Mutations in this gene are associated with congenital disorder of glycosylation type Iq. For more details, click here

Synonyms: Congenital Disorder of Glycosylation Type Iq, Coloboma, Ocular, with Ichthyosis, Brain Malformations, and Endocrine Abnormalities, CDGIq, Congenital disorder of glycosylation due to steroid 5alpha-reductase type 3 deficiency, CDG-Iq, Congenital disorder of glycosylation type 1q, Congenital disorder of glycosylation type Iq, SRD5A3-CDG, CDG syndrome type Iq. For more details, click here.

SRD5A3 plays a key role in early steps of protein N-linked glycosylation by being required for the conversion of polyprenol into dolichol. Dolichols are required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-glycosylation. Acts as a polyprenol reductase that promotes the reduction of the alpha-isoprene unit of polyprenols into dolichols in a NADP-dependent mechanism. Also able to convert testosterone (T) into 5-alpha-dihydrotestosterone (DHT). For more details click here

SRD5A3-CDG (also known as CDG syndrome type Iq, CDG-Iq, CDG1Q or Congenital disorder of glycosylation type 1q) is a rare, non X-linked congenital disorder of glycosylation (CDG)[1] due to a mutation in the steroid 5 alpha reductase type 3 gene. It is one of over 150 documented types of Congenital disorders of Glycosylation[2]. Like many other CDGs, SRD5A3 is ultra-rare, with around 38 documented cases in the world.[3]  For more details click here