case_images: PMC11153700_01
case_images: Primary Care Pedigree. At the PCPM clinic, genetic counselors meticulously compile comprehensive family histories, encompassing diverse medical conditions. This thorough examination enables healthcare providers to pinpoint specific areas warranting further genetic investigation. Analyzing the proband's pedigree, supplied by the patient's mother, reveals a notable familial prevalence of thyroid disease and heart conditions. However, there is a distinct absence of intellectual disability or neurodevelopmental disorders present in the family, hinting that there is a novel reason for the patient's symptoms. Arrow indicates proband (patient). Abbreviations: ADHD, attention deficit hyperactivity disorder; ALZ, Alzheimer's disease; ANX, anxiety; ASD, autism spectrum disorder; A&W, alive and well; HHT, hereditary hemorrhagic telangiectasia; HT, Hashimoto's thyroiditis; HTN, hypertension; LD, learning difficulty; OA, osteoarthritis; OCD, obsessive-compulsive disorder; PANDAS, pediatric autoimmune neuropsychiatric disorders associated with recurrent streptococcal infections; PCOS, polycystic ovary syndrome; PVC, premature ventricular contraction; RA, rheumatoid arthritis; T2DM, Type II diabetes mellitus; TD, thyroid disease. Created with BioRender.com.
case_images: fgene-15-1380552-g001.jpg
case_images: PMC11153700_01_fgene-15-1380552-g001.jpg
case_images: F1
case_images: See full pedigree (Figure 1).
case_images: Diagnostic Timeline. At 15, the patient underwent genetic tests for neurodevelopmental symptoms without diagnostic yield. Referral to the PCPM clinic led to Whole Exome Sequencing (WES), unveiling a pathogenic HNRNPU mutation. WES data informed two subsequent genetic inquiries. Created with BioRender.com.
case_images: fgene-15-1380552-g002.jpg
case_images: PMC11153700_02_fgene-15-1380552-g002.jpg
case_images: F2
case_images: Reanalysis was completed on the data and no additional variants were found (Figures 2, 3B), thus the patient's intermittent elevated serum iron concentration remains unexplained. The main causal HHT genes were evaluated (ACVRL1, ENG, and SMAD4), which revealed no pathogenic variations (Figures 2, 3B).
case_images: Genetic Testing Overview. (A) Before the patient's evaluation at the PCPM clinic, numerous genetic tests were conducted, all proving uninformative. (B) Following intake at the clinic, Whole Exome Sequencing (WES) was initiated, leading to a conclusive diagnosis for the patient and her family. Importantly, the WES data was leveraged to address two more genetic inquiries, obviating the necessity for supplementary testing. Created with BioRender.com.
case_images: fgene-15-1380552-g003.jpg
case_images: PMC11153700_02_fgene-15-1380552-g003.jpg
case_images: F3
case_images: Reanalysis was completed on the data and no additional variants were found (Figures 2, 3B), thus the patient's intermittent elevated serum iron concentration remains unexplained. The main causal HHT genes were evaluated (ACVRL1, ENG, and SMAD4), which revealed no pathogenic variations (Figures 2, 3B).
case_images: PMC11153700_02
case_images: Diagnostic Timeline. At 15, the patient underwent genetic tests for neurodevelopmental symptoms without diagnostic yield. Referral to the PCPM clinic led to Whole Exome Sequencing (WES), unveiling a pathogenic HNRNPU mutation. WES data informed two subsequent genetic inquiries. Created with BioRender.com.
case_images: fgene-15-1380552-g002.jpg
case_images: PMC11153700_02_fgene-15-1380552-g002.jpg
case_images: F2
case_images: Reanalysis was completed on the data and no additional variants were found (Figures 2, 3B), thus the patient's intermittent elevated serum iron concentration remains unexplained. The main causal HHT genes were evaluated (ACVRL1, ENG, and SMAD4), which revealed no pathogenic variations (Figures 2, 3B).
case_images: Genetic Testing Overview. (A) Before the patient's evaluation at the PCPM clinic, numerous genetic tests were conducted, all proving uninformative. (B) Following intake at the clinic, Whole Exome Sequencing (WES) was initiated, leading to a conclusive diagnosis for the patient and her family. Importantly, the WES data was leveraged to address two more genetic inquiries, obviating the necessity for supplementary testing. Created with BioRender.com.
case_images: fgene-15-1380552-g003.jpg
case_images: PMC11153700_02_fgene-15-1380552-g003.jpg
case_images: F3
case_images: Reanalysis was completed on the data and no additional variants were found (Figures 2, 3B), thus the patient's intermittent elevated serum iron concentration remains unexplained. The main causal HHT genes were evaluated (ACVRL1, ENG, and SMAD4), which revealed no pathogenic variations (Figures 2, 3B).