Identification of a case of SRD5A3-congenital disorder of glycosylation (CDG1Q) by exome sequencing

Gupta, Neerja; Verma, Gaurav; Kabra, Madhulika; Bijarnia‐Mahay, Sunita; Ganapathy, Aparna

doi:10.4103/ijmr.ijmr_820_16

Cited by 10 publications

(18 citation statements)

References 19 publications

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“…SRD5A3-CDG is an autosomal recessive disorder, though interestingly, in our cohort, all our families have affected siblings, where four out of five sibships were duos, and one family presented with three affected children. The commonest SRD5A3-CDG mutation reported so far is c.57G > A p.(Trp19Ter) p.W19X , also found in seven patients in our cohort ( Morava et al, 2010 ; Gründahl et al, 2012 ; Kara et al, 2014 ; Tuysuz et al, 2016 ; Taylor et al, 2017 ; Gupta et al, 2018 ). These families are of Kurdish, Indian, or Pakistani background.…”

Section: Resultssupporting

confidence: 62%

SRD5A3-CDG: Emerging Phenotypic Features of an Ultrarare CDG Subtype

et al. 2021

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Background: SRD5A3-CDG is a rare N-glycosylation defect caused by steroid 5 alpha reductase type 3 deficiency. Its key feature is an early severe visual impairment with variable ocular anomalies often leading to diagnosis. Additional symptoms are still poorly defined. In this case study, we discuss 11 genetically confirmed cases, and report on emerging features involving other systems in addition to the eye phenotype.Methods: In total, 11 SRD5A3-CDG patients in five sets of sibships were included in the study. Data on 9 of 11 patients are as of yet unpublished. Patients’ results on biochemical and genetic investigations and on in-depth phenotyping are presented.Results: Key diagnostic features of SRD5A3-CDG are ophthalmological abnormalities with early-onset retinal dystrophy and optic nerve hypoplasia. SRD5A3-CDG is also characterized by variable neurological symptoms including intellectual disability, ataxia, and hypotonia. Furthermore, ichthyosiform skin lesions, joint laxity, and scoliosis have been observed in our cohort. We also report additional findings including dystonia, anxiety disorder, gastrointestinal symptoms, and MRI findings of small basal ganglia and mal-rotated hippocampus, whereas previous publications described dysmorphic features as a common finding in SRD5A3, which could not be confirmed in our patient cohort.Conclusion: The detailed description of the phenotype of this large cohort of patients with SRD5A3-CDG highlights that the key clinical diagnostic features of SRD5A3-CDG are an early onset form of ophthalmological problems in patients with a multisystem disorder with variable symptoms evolving over time. This should aid earlier diagnosis and confirms the need for long-time follow-up of patients.

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Section: Resultssupporting

confidence: 62%

SRD5A3-CDG: Emerging Phenotypic Features of an Ultrarare CDG Subtype

et al. 2021

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“…Severe intellectual disability was observed in all SRD5A3‐CDG patients whereas lower normal intelligence was exceptional (Kara et al, 2014). Epilepsy which is a main concern in other forms of CDG was uncommon in SRD5A3‐CDG cases and was noticed in 7/38 patients with absence, generalized tonic–clonic seizures and west syndrome (Al‐Sarraj et al, 2014; Gupta et al, 2018; Wheeler et al, 2016). It is worth notably to mention that none of our patients had seizures at all.…”

Section: Discussionmentioning

confidence: 99%

“…We have customized a recognition system based on deep learning of residual CNN Architecture (ResNet) to extract the most relevant facial features from frontal 2D images of SRD5A3‐CDG cases. In addition to our patient's photos, all images from published SRD5A3‐CDG cases were used for this purpose (Al‐Gazali, Hertecant, Algawi, El Teraifi, & Dattani, 2008; Al‐Sarraj et al, 2014; Bastaki et al, 2018; Chang, He, & Lam, 2018; Gupta et al, 2018; Kahrizi et al, 2009; Kasapkara et al, 2012; Medrano et al, 2019; Eva Morava et al, 2010; Taylor et al, 2017; Tuysuz et al, 2015; Wheeler et al, 2016). Given the limited number of available photos in our database, data augmentation approach was adopted where each image was randomly augmented through rotation with a range of −10 to 10°.…”

Section: Methodsmentioning

confidence: 99%

“…Cantagrel et al (2010) identified the first SRD5A3 homozygous pathogenic variant in a large Emirati family. Subsequently, 17 SRD5A3‐CDG‐causing variants were identified in 26 families (Al‐Sarraj et al, 2014; Bastaki et al, 2018; Gründahl et al, 2012; Gupta, Verma, Kabra, Bijarnia‐Mahay, & Ganapathy, 2018; Kahrizi et al, 2009, 2011; Kara, Ayhan, Gökçay, Başboğaoğlu, & Tolun, 2014; Kasapkara et al, 2012; Kousal et al, 2019; Medrano et al, 2019; E. Morava et al, 2008; Eva Morava et al, 2010; Najmabadi et al, 2011; Taylor et al, 2017; Tuysuz et al, 2015; Wheeler et al, 2016). Most of those variants are either of nonsense or frameshift.…”

Section: Introductionmentioning

confidence: 99%

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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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“…Only 38 cases of this disease have been reported worldwide, presenting with a highly variable phenotype. While ataxia is mentioned in just under half of these cases, telangiectasia is yet to be reported (2,3).…”

Section: Introductionmentioning

confidence: 99%

A rare case of SRD5A3-CDG in a patient with ataxia and telangiectasia: A case report

nabavizadeh

Noeiaghdam

Johari

et al. 2022

Preprint

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SRD5A3-CDG (MIM 612379) is an extremely rare congenital disease, with only 38 cases having been reported. Common manifestations are developmental delay, intellectual disability, ophthalmological abnormalities, cerebellar abnormalities, ataxia, and hypotonia. Here, we discuss a seven-year-old boy with SRD5A3-CDG (homozygous variant c.57G>A [p.Trp19Ter]), featuring the unprecedented finding of telangiectasia.

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Identification of a case of SRD5A3-congenital disorder of glycosylation (CDG1Q) by exome sequencing

Cited by 10 publications

References 19 publications

SRD5A3-CDG: Emerging Phenotypic Features of an Ultrarare CDG Subtype

SRD5A3-CDG: Emerging Phenotypic Features of an Ultrarare CDG Subtype

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

A rare case of SRD5A3-CDG in a patient with ataxia and telangiectasia: A case report

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