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. 2021 Apr;185(4):1081-1090.
doi: 10.1002/ajmg.a.62065. Epub 2021 Jan 6.

SRD5A3-CDG: 3D structure modeling, clinical spectrum, and computer-based dysmorphic facial recognition

Ikhlas Ben Ayed  1   2   3 , Wael Ouarda  4 , Fakher Frikha  5 , Fatma Kammoun  6   7 , Amal Souissi  1 , Mariem Ben Said  1 , Amal Bouzid  1 , Ines Elloumi  1 , Tarak M Hamdani  4 , Nourhene Gharbi  2   3 , Nesrine Baklouti  4 , Manel Guirat  2 , Fatma Mejdoub  2 , Najla Kharrat  1 , Imene Boujelbene  2   3 , Fatma Abdelhedi  2   3 , Neila Belguith  3   8   9 , Leila Keskes  3   8 , Abdullah Ahmed Gibriel  10 , Hassen Kamoun  2   3 , Chahnez Triki  6   7 , Adel M Alimi  4 , Saber Masmoudi  1
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SRD5A3-CDG: 3D structure modeling, clinical spectrum, and computer-based dysmorphic facial recognition

Ikhlas Ben Ayed et al. Am J Med Genet A. 2021 Apr.

Abstract

Pathogenic variants in Steroid 5 alpha reductase type 3 (SRD5A3) cause rare inherited congenital disorder of glycosylation known as SRD5A3-CDG (MIM# 612379). To date, 43 affected individuals have been reported. Despite the development of various dysmorphic features in significant number of patients, facial recognition entity has not yet been established for SRD5A3-CDG. Herein, we reported a novel SRD5A3 missense pathogenic variant c.460 T > C p.(Ser154Pro). The 3D structural modeling of the SRD5A3 protein revealed additional transmembrane α-helices and predicted that the p.(Ser154Pro) variant is located in a potential active site and is capable of reducing its catalytic efficiency. Based on phenotypes of our patients and all published SRD5A3-CDG cases, we identified the most common clinical features as well as some recurrent dysmorphic features such as arched eyebrows, wide eyes, shallow nasal bridge, short nose, and large mouth. Based on facial digital 2D images, we successfully designed and validated a SRD5A3-CDG computer based dysmorphic facial analysis, which achieved 92.5% accuracy. The current work integrates genotypic, 3D structural modeling and phenotypic characteristics of CDG-SRD5A3 cases with the successful development of computer tool for accurate facial recognition of CDG-SRD5A3 complex cases to assist in the diagnosis of this particular disorder globally.

Keywords: 3D structure modeling; congenital disorders of glycosylation; exome-clinical sequencing; facial recognition; polyprenol reductase.

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References

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