SRD5A3-CDG: Twins with an intragenic tandem duplication

Rieger M, Türk M, Kraus C, Uebe S, Ekici AB, Krumbiegel M, Huchzermeyer C, Wiesmann da Silva Reis A, Thiel C (2022)

Publication Type: Journal article

Publication year: 2022


Book Volume: 65

Article Number: 104492

Journal Issue: 5

DOI: 10.1016/j.ejmg.2022.104492


Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a rare metabolic disease mainly characterized by psychomotor disability, visual impairment, and variable eye malformations caused by bi-allelic pathogenic variants in SRD5A3. So far, only 23 distinct mutations were described. Exome sequencing in 32-year old monozygotic male twins revealed only the heterozygous splice variant c.562+3delG in SRD5A3, but no second variant. The twins presented with psychomotor deficit and a complex eye disease including retinal dystrophy, pallor of the papilla, nystagmus, and strabismus suggestive of SRD5A3-CDG. Only when applying exome-based copy number analysis, we identified as a second compound heterozygous variant a previously not reported tandem duplication of exons 2–4 in SRD5A3. Next to the typical skeletal anomalies of SRD5A3-CDG such as kyphosis and scoliosis, extension deficits of the proximal interphalangeal (PIP) joints IV were observed. Since similar contractures were described once in a patient with SRD5A3-CDG, we suggest that this rare symptom is possibly associated with SRD5A3-CDG. Our findings further expand the mutational and clinical spectrum of SRD5A3-CDG and emphasize the importance of an intragenic copy number analysis in patients with strong clinical suspicion of SRD5A3-CDG and only one detectable sequence variant.

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How to cite


Rieger, M., Türk, M., Kraus, C., Uebe, S., Ekici, A.B., Krumbiegel, M.,... Thiel, C. (2022). SRD5A3-CDG: Twins with an intragenic tandem duplication. European Journal of Medical Genetics, 65(5).


Rieger, Melissa, et al. "SRD5A3-CDG: Twins with an intragenic tandem duplication." European Journal of Medical Genetics 65.5 (2022).

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