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

3-Oxo-5-alpha-Steroid 4-Dehydrogenase / genetics Abnormalities, Multiple / genetics Adolescent Cataract / complications Child Child, Preschool Congenital Disorders of Glycosylation / complications Eye / pathology Facial Recognition Facies Female Humans Membrane Proteins / genetics Muscular Atrophy / complications Mutation, Missense / genetics

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

Journal

American journal of medical genetics. Part A

ISSN: 1552-4833

Titre abrégé: Am J Med Genet A

Pays: United States

ID NLM: 101235741

Informations de publication

Date de publication:
04 2021

Historique:

revised: 02 12 2020

received: 23 07 2020

accepted: 14 12 2020

pubmed: 7 1 2021

medline: 7 8 2021

entrez: 6 1 2021

Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1002/ajmg.a.62065 PMID: 33403770

pubmed: 33403770

doi: 10.1002/ajmg.a.62065

doi:

Substances chimiques

Membrane Proteins 0

3-Oxo-5-alpha-Steroid 4-Dehydrogenase EC 1.3.99.5

SRD5A3 protein, human EC 1.3.99.5

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

1081-1090

Informations de copyright

Références

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