Original Article
Published: Jun 30, 2025 | DOI: 10.24911/JBCGenetics.183-1735648400
Non-syndromic intellectual disability and cataract in a patient with dual molecular diagnosis of SRD5A3 and PITX3-related diseases
Authors: Naif A.M. Almontashiri , Samar A. Al-Swailem , Reham M. Balahmar , Essa Alharby , Manar M. Almuntashri , Ali Alasmari
Article Info
Authors
Naif A.M. Almontashiri
Center for Genetics and Inherited Diseases, Taibah University, Almadinah Almunwarah, Saudi Arabia
Samar A. Al-Swailem
Anterior Segment Division, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia
Reham M. Balahmar
Center for Genetics and Inherited Diseases, Taibah University, Almadinah Almunwarah, Saudi Arabia
Essa Alharby
Center for Genetics and Inherited Diseases, Taibah University, Almadinah Almunwarah, Saudi Arabia
Manar M. Almuntashri
King Saud University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical city and Ministry of National Guard, Riyadh, Saudi Arabia
Ali Alasmari
Section of Medical Genetics, Children’s Specialist Hospital, King Fahad Medical City, Riyadh, Saudi Arabia
Publication History
Received: December 31, 2024
Accepted: June 30, 2025
Published: June 30, 2025
Abstract
Objectives: Our objective was to identify the genetic cause in a patient with intellectual disability and bilateral cataracts.
Methods: The genetic, neurological, and ophthalmological evaluations were performed. DNA samples were provided from the patient, parents, and unaffected sibs to perform whole exome sequencing (WES) and Sanger confirmation. Biochemical testing on the serum sample was performed to ascertain the clinical significance of the WES finding.
Results: The proband presented with intellectual disability, subtle dysmorphic features, and bilateral cataracts. WES and segregation studies using Sanger sequencing revealed a homozygous missense variant of uncertain significance (VUS) in SRD5A3 and a de novo pathogenic frameshift variant in PITX3 in the proband. Biochemical analysis of serum carbohydrate-deficient-transferrin (CDT) to ascertain the significance of the VUS in SRD5A3 was consistent with a glycosylation defect and confirmed type 1, N-glycosylation defect.
Conclusion: This case has a dual molecular diagnosis. The SRD5A3 variant with confirmed biochemical abnormality accounts for intellectual disability and subtle dysmorphic features, whereas the de novo pathogenic PITX3 variant accounts for bilateral cataracts. This case expands the severity spectrum of SRD5A3 disorder and represents a milder form. It also highlights the importance of clinical correlation and reverse phenotyping.
Keywords: CDG1Q, congenital disorder of glycosylation, type Iq, CDT, carbohydrate-deficient-transferrin.
Pubmed Style
Naif A.M. Almontashiri, Samar A. Al-Swailem, Reham M. Balahmar, Essa Alharby, Manar M. Almuntashri, Ali Alasmari. Non-syndromic intellectual disability and cataract in a patient with dual molecular diagnosis of SRD5A3 and PITX3-related diseases. JBC Genetics. 2025; 30 (June 2025): -. doi:10.24911/JBCGenetics.183-1735648400
Web Style
Naif A.M. Almontashiri, Samar A. Al-Swailem, Reham M. Balahmar, Essa Alharby, Manar M. Almuntashri, Ali Alasmari. Non-syndromic intellectual disability and cataract in a patient with dual molecular diagnosis of SRD5A3 and PITX3-related diseases. https://www.jbcgenetics.com/articles/2295 [Access: July 31, 2025]. doi:10.24911/JBCGenetics.183-1735648400
AMA (American Medical Association) Style
Naif A.M. Almontashiri, Samar A. Al-Swailem, Reham M. Balahmar, Essa Alharby, Manar M. Almuntashri, Ali Alasmari. Non-syndromic intellectual disability and cataract in a patient with dual molecular diagnosis of SRD5A3 and PITX3-related diseases. JBC Genetics. 2025; 30 (June 2025): -. doi:10.24911/JBCGenetics.183-1735648400
Vancouver/ICMJE Style
Naif A.M. Almontashiri, Samar A. Al-Swailem, Reham M. Balahmar, Essa Alharby, Manar M. Almuntashri, Ali Alasmari. Non-syndromic intellectual disability and cataract in a patient with dual molecular diagnosis of SRD5A3 and PITX3-related diseases. JBC Genetics. (2025), [cited July 31, 2025]; 30 (June 2025): -. doi:10.24911/JBCGenetics.183-1735648400
Harvard Style
Naif A.M. Almontashiri, Samar A. Al-Swailem, Reham M. Balahmar, Essa Alharby, Manar M. Almuntashri, Ali Alasmari (2025) Non-syndromic intellectual disability and cataract in a patient with dual molecular diagnosis of SRD5A3 and PITX3-related diseases. JBC Genetics, 30 (June 2025): -. doi:10.24911/JBCGenetics.183-1735648400
Chicago Style
Naif A.M. Almontashiri, Samar A. Al-Swailem, Reham M. Balahmar, Essa Alharby, Manar M. Almuntashri, Ali Alasmari. "Non-syndromic intellectual disability and cataract in a patient with dual molecular diagnosis of SRD5A3 and PITX3-related diseases." 30 (2025), -. doi:10.24911/JBCGenetics.183-1735648400
MLA (The Modern Language Association) Style
Naif A.M. Almontashiri, Samar A. Al-Swailem, Reham M. Balahmar, Essa Alharby, Manar M. Almuntashri, Ali Alasmari. "Non-syndromic intellectual disability and cataract in a patient with dual molecular diagnosis of SRD5A3 and PITX3-related diseases." 30.June 2025 (2025), -. Print. doi:10.24911/JBCGenetics.183-1735648400
APA (American Psychological Association) Style
Naif A.M. Almontashiri, Samar A. Al-Swailem, Reham M. Balahmar, Essa Alharby, Manar M. Almuntashri, Ali Alasmari (2025) Non-syndromic intellectual disability and cataract in a patient with dual molecular diagnosis of SRD5A3 and PITX3-related diseases. , 30 (June 2025), -. doi:10.24911/JBCGenetics.183-1735648400