Review of SRD5A3 Disease-Causing Sequence Variants and Ocular Findings in Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation, and a Detailed New Case

Kousal, B.; Honzík, T.; Hansíková, H.; Ondrušková, N.; Čechová, A.; Tesařová, M.; Stránecký, V.; Meliška, M.; Michaelides, M.; Lišková, Petra

doi:10.14712/fb2019065030134

Cited by 12 publications

(2 citation statements)

References 19 publications

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“…Nine patients presented microcytic anemia, transient hypertransaminasemia and coagulation abnormalities. Variable eye and skin involvement are predominant (107)(108)(109)(110). STT3B-CDG (CDG-Ix, OMIM #615597).…”

Section: Resultsmentioning

confidence: 99%

Liver Involvement in Congenital Disorders of Glycosylation: A Systematic Review

Colantuono

D’Acunto

Melis

et al. 2021

Journal of Pediatric Gastroenterology &Amp; Nutrition

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An ever-increasing number of disturbances in glycosylation have been described to underlie certain unexplained liver diseases presenting either almost isolated or in a multi-organ context. We aimed to update previous literature screenings which had identified up to 23 forms of congenital disorders of glycosylation (CDG) with associated liver disease. We conducted a comprehensive literature search of three scientific electronic databases looking at articles published during the last 20 years (January 2000-October 2020). Eligible studies were case reports/series reporting liver involvement in CDG patients. Our systematic review led us to point out 41 forms of CDG where the liver is primarily affected (n ¼ 7) or variably involved in a multisystem disease with mandatory neurological abnormalities (n ¼ 34). Herein we summarize individual clinical and laboratory presentation characteristics of these 41 CDG and outline their main presentation and diagnostic cornerstones with the aid of two synoptic tables. Dietary supplementation strategies have hitherto been investigated only in seven of these CDG types with liver disease, with a wide range of results. In conclusion, the systematic review recognized a liver involvement in a somewhat larger number of CDG variants corresponding to about 30% of the total of CDG so far reported, and it is likely that the number may increase further. This information could assist in an earlier correct diagnosis and a possibly proper management of these disorders.

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Section: Resultsmentioning

confidence: 99%

Liver Involvement in Congenital Disorders of Glycosylation: A Systematic Review

Colantuono

D’Acunto

Melis

et al. 2021

Journal of Pediatric Gastroenterology &Amp; Nutrition

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“…SRD5A2 has (4%) overexpression which involve in androgen sensitivity in prostate tissue. SRD5A3 has (2.2%) overexpression which involve in regulation of androgen receptor pathway (Tosi et al, 2011;Batista & Mendonca, 2020;Kousal et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

CYP17A1 Network Analysis in Ovarian Serous Cystadenocarcinoma for Retrieval of Polycystic ovaries Targets

Shah,

Tayyab

2024

Albus Scientia

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Background/Aims: CYP17A1 is great metabolic switch for androgen overproduction which is hallmark of polycystic ovary syndrome (PCOS)initiation and progression. There is an urgent need to determine CYP17A1 mediated set of metabolic therapeutic targets for PCOS to control androgen synthesis with wide range of molecular options. Methodology: We apply rational in silico approach for determination of PCOS comprehensive set of drug targets. First, we retrieve CYP17A1 network dataset from STRING database (https://string-db.org/) by querying CYP17A1 name that gives us updated 30 nodes containing network with unique options of enrichment analysis and module extraction. The enrichment analysis determines CYP17A1 network involvement in steroidogenesis process with carcinogenesis and drug metabolism. We select ovarian serous cystadenocarcinoma dataset from cBioPortal server (https://www.cbioportal.org/) for CYP17A1 network differential analysis. Results: In this study, several steroid synthesis pathway members showed overexpression including SRD5A1, AKR1C3, CYP11B1, CYP11B2, CYP7A1, AKR1C1, AKR1D1, CYP7B1, CYP21A2, POR and HSD17B8 and are ideal biomarkers that provide cell cycle energy requirements for ovarian carcinoma. Few anti-androgenic members such as HSD17B2, STS, SULT2B1 and CYB5A showed down regulation that predicts the impact of hyper androgenemia on carcinogenesis. Drug metabolism components also showed up regulation which can be potential biomarkers for drug resistance in chemotherapies. Conclusion: Our work suggests androgen and its synthesis pathway paramount in tumorigenesis and is an excellent therapeutic target in ovarian carcinoma. In future, validation of CYP17A1 network as a signature in both ovarian serous cystadenocarcinoma and PCOS dataset may lead to novel shared therapeutic combinations and tremendous syndrome-syndrome molecular linkage for personalized medicine.

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SRD5A3‐CDG:3Dstructure modeling, clinical spectrum, andcomputer‐baseddysmorphic facial recognition

Ayed

Ouarda

Frikha

et al. 2021

American J of Med Genetics Pt A

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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.

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Review of SRD5A3 Disease-Causing Sequence Variants and Ocular Findings in Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation, and a Detailed New Case

Cited by 12 publications

References 19 publications

Liver Involvement in Congenital Disorders of Glycosylation: A Systematic Review

Liver Involvement in Congenital Disorders of Glycosylation: A Systematic Review

CYP17A1 Network Analysis in Ovarian Serous Cystadenocarcinoma for Retrieval of Polycystic ovaries Targets

SRD5A3‐CDG:3Dstructure modeling, clinical spectrum, andcomputer‐baseddysmorphic facial recognition

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