Publications by authors named "Rizwan Hamid"
Background: The number of known inherited metabolic diseases (IMDs) has been expanding, and the rate of diagnosis is improving with the development of innovative approaches including next generation sequencing (NGS). However, a substantial proportion of IMDs remain undetected by traditional diagnostic approaches. We aim to highlight the spectrum of IMDs diagnosed by the Undiagnosed Diseases Network (UDN) and to learn from the UDN diagnostic processes that were able to detect IMDs.
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- Autosomal dominant congenital disorder of glycosylation (CDG) type Iw is caused by a mutation in a specific gene and differs from most CDGs, which are typically autosomal recessive.
- A 17-year-old male presented with a range of symptoms including macrocephaly, epilepsy, and developmental delays, but initial genetic tests and biochemical analyses did not indicate a clear diagnosis.
- Genome sequencing revealed a novel mutation that disrupts a glycosylation site, and the patient was ultimately diagnosed with CDG type Iw based on abnormal transferrin profiling, illustrating the variability in genetic disorders and the need for comprehensive testing.
Purpose: Variants in result in a rare neurodevelopmental disorder characterized by a variable clinical presentation of symptoms including developmental delay, epilepsy, motor dysfunction, and autism spectrum disorder. haploinsufficiency has been confirmed as the predominant pathway of related neurodevelopmental disorders (NDDs), however, the molecular mechanism underlying the variable clinical presentation remains unclear.
Methods: Here, through work of the Undiagnosed Diseases Network, we identify an undiagnosed individual with an inherited p.
Article Synopsis
- Phenotyping is essential for diagnosing and treating rare diseases, but current methods rely on unstructured text, which requires annotated data for effective analysis.
- This study investigates the use of prompt learning with ChatGPT for identifying rare disease phenotypes, comparing its performance to fine-tuning with BioClinicalBERT.
- Results show that while fine-tuning BioClinicalBERT performs better overall, ChatGPT can match its accuracy with just one annotated sample, suggesting a promising approach for easier extraction of rare disease information.
Article Synopsis
- - The SATURN registry, a European multicenter study, aims to evaluate the effectiveness of surgical devices for treating male stress urinary incontinence, focusing on cure rates during a 10-year follow-up, with 1-year results currently reported.
- - The study involved 1,046 male patients, primarily post-radical prostatectomy, using various implants like AMS800 and Advance, and showed varying self-reported continence rates—ranging from 11% to 76% depending on the device, with 32% of patients still experiencing incontinence after one year.
- - Patient-reported outcomes indicated improvements in quality of life, but a notable percentage of patients required revisions of their devices, suggesting complications remained a concern
Article Synopsis
- The 2024 EAU guidelines for neurourology emphasize the importance of lifelong management for patients with neurological conditions affecting urinary, sexual, and bowel functions.
- The guidelines were updated based on a literature review from 2021-2023, with evidence and strength ratings assigned to each recommendation to ensure a comprehensive approach to diagnosis and treatment.
- Key recommendations include early diagnosis, customized management plans involving multidisciplinary care, and continuous follow-up to maintain patients' quality of life.
Article Synopsis
- The Undiagnosed Disease Network (UDN) is a collaborative effort funded by the NIH, focused on diagnosing rare diseases through 12 clinical sites, including Vanderbilt University Medical Center (VUMC).
- At VUMC, experts in fields like bioinformatics, structural biology, and genetics worked together to identify a rare genetic variant in a 5-year-old girl with various neurological issues.
- The team diagnosed her with Primary Aldosteronism, Seizures, and Neurologic abnormalities (PASNA), showcasing the value of a multidisciplinary approach in addressing complex, rare diseases.
Article Synopsis
- Recent research identified a new mutation linked to a rare axonal Charcot-Marie-Tooth disease in both Caucasian and black African families, expanding the understanding of its genetic basis.
- The study involved eight patients and their relatives, with a diagnosis average age of 33.9 years; common symptoms included walking difficulties, muscle weakness, and deformities in hands and feet.
- Whole exome sequencing uncovered a novel variant in the gene responsible, revealing notable decreases in protein levels and structural changes, emphasizing the importance of including diverse populations in genetic research.
Article Synopsis
- - Surgery for male incontinence with artificial urinary sphincters and slings (SATURN) is an observational study aimed at gathering data on male stress urinary incontinence surgeries across various European centers.
- - The registry will assess both short- and long-term outcomes of these surgeries, focusing on their effectiveness and how they affect patients' quality of life.
- - By collecting this prospective data, the study aims to improve understanding and treatment strategies for male urinary incontinence.
Article Synopsis
- - A 26-year-old woman diagnosed with Diamond-Blackfan anemia (DBA) was referred to the Undiagnosed Diseases Network due to the lack of a specific genetic cause found for her condition.
- - Her case was uniquely identified as being influenced by digenic interactions, specifically involving variations in two different genes (RPS19 and RPL27), rather than the typical single-gene mutations usually associated with DBA.
- - The findings were supported by advanced techniques including machine learning models, co-segregation analysis, and RNA sequencing, highlighting that atypical presentations of DBA may arise from multiple gene interactions and not just single-gene effects.
Article Synopsis
- A 72-year-old man with 45 years of progressive weakness in his legs was initially misdiagnosed with Charcot-Marie-Tooth disease type 2 (CMT2) but didn't have a clear genetic cause identified.
- After exome sequencing (ES) failed to pinpoint a problem, further investigation revealed biallelic variants in the sorbitol dehydrogenase (SORD) gene, leading to a formal diagnosis of Sorbitol Dehydrogenase Deficiency with Peripheral Neuropathy (SORDD).
- The patient's diagnosis allowed him to participate in a clinical trial for a potential new treatment, highlighting the importance of advanced genetic testing for accurate diagnosis in similar cases.
Article Synopsis
- The study explores the effectiveness of onabotulinumtoxinA (onabotA) as an alternative treatment for patients with overactive bladder (OAB) who have not responded to oral medications, based on findings from the GRACE study.
- A subanalysis assessed patients who previously used one or more anticholinergics or β-3 adrenoreceptor agonists, with safety monitored for 12 months and efficacy evaluated over 12 weeks.
- Results showed significant reductions in urinary incontinence, urgency, and other symptoms after treatment with onabotA, regardless of the patient's prior medication history, indicating its potential as an effective option for managing OAB.
Article Synopsis
- - The study explores the role of mosaicism in genetic diseases and how it relates to disease-causing variants that arise spontaneously (de novo variants) in families, involving data from nearly 15,000 individuals.
- - Researchers found that about 4.51% of individuals with confirmed genetic diseases showed mosaic genetic disease (MGD), and approximately 2.86% of parents had parental mosaicism, especially in cases involving de novo variants.
- - The findings highlight the complexity and variability of MGD, suggesting it contributes significantly to genetic disorders, although further investigation is needed to better understand its implications for diagnoses and familial risks.
Article Synopsis
- - We analyze a case of a 20-year-old male with an unidentified neurodegenerative disease who had a severe deficiency in nicotinamide intermediates, crucial for NAD(H) biosynthesis.
- - Metabolic profiling tests showed that the patient's nicotinamide N-methyltransferase (NNMT) enzyme was not active during normal feeding or fasting but became functional after a specific nicotinamide intake.
- - This case represents a unique instance of adult-onset NNMT deficiency linked to neurodegenerative disease, highlighting the role of metabolomics in identifying rare metabolic disorders.
Article Synopsis
- * Key gaps in research include understanding the impacts of NLUTD on sexual and bowel function, assessing renal function in those with limited mobility, and establishing effective guidelines for low-resource settings.
- * The authors advocate for a global, unified approach to develop comprehensive, resource-independent guidelines for NLUTD and related issues, highlighting the need for targeted research to address existing evidence gaps.
Article Synopsis
- * This is especially critical for patients from underrepresented groups, who often face higher rates of uncertain genetic findings.
- * The text outlines key challenges and proposes solutions for a systematic approach to genetic variant reinterpretation, including infrastructure needs, patient consent, triggering processes, data flow, cost coverage, and implementation policies.
Article Synopsis
- Ewing's sarcoma (ES) is a malignant bone tumor, the second most common type in children, usually presenting as swelling followed by pain.
- It is aggressive, with rapid growth and metastasis, and can be misdiagnosed due to its rare occurrence in the jaw area, often mistaken for an odontogenic infection.
- The case of a 13-year-old girl highlights the importance of recognizing ES to prevent delays in diagnosis and potential negative outcomes.
Molecular Function and Contribution of in Development and Disease.
Am J Respir Crit Care Med
April 2023
Article Synopsis
- - Recent studies highlight the significant role of the () gene in respiratory diseases, linking its variants to congenital disorders that affect the respiratory and skeletal systems.
- - The exact impact of the () gene on human development is still unclear, prompting a closer look at its developmental, tissue-specific, and pathological roles based on both human and animal research.
- - The text calls for further research to better understand the () gene's functions and the consequences of its disruption on development and health.
Article Synopsis
- Whole-exome sequencing (WES) has identified rare monogenic developmental and epileptic encephalopathies (DEE) linked to ion channel variants, but often struggles with interpreting variants of unknown significance (VUS).
- The study introduces a "personalized structural biology" (PSB) approach that uses protein 3D structure analysis to interpret these VUS more effectively.
- By investigating two nearby variants in the Kv3.2 potassium channel, researchers demonstrate how one variant blocks the channel while the other stabilizes its open state, highlighting the utility of PSB in making sense of complex genetic data for DEE cases.
Article Synopsis
- - The study aimed to assess the effectiveness of ona-botulinum toxin A (BTX-A) injections into the external urethral sphincter for women suffering from voicing dysfunction due to nonneurogenic nonrelaxing sphincter issues.
- - A group of 35 female patients (average age 37.5) was examined after receiving BTX-A; results showed significant improvements, with 60% able to void normally and increased flow rates after treatment.
- - Predictors of successful outcomes included high preoperative postvoid residuals and prior surgeries, with about 46% of patients opting for repeat injections after experiencing an average symptom relief duration of 4.7 months.
Purpose: The knowledge used to classify genetic variants is continually evolving, and the classification can change on the basis of newly available data. Although up-to-date variant classification is essential for clinical management, reproductive planning, and identifying at-risk family members, there is no consistent practice across laboratories or clinicians on how or under what circumstances to perform variant reinterpretation.
Methods: We conducted exploratory focus groups (N = 142) and surveys (N = 1753) with stakeholders involved in the process of variant reinterpretation (laboratory directors, clinical geneticists, genetic counselors, nongenetic providers, and patients/parents) to assess opinions on key issues, including initiation of reinterpretation, variants to report, termination of the responsibility to reinterpret, and concerns about consent, cost, and liability.
Article Synopsis
- Rare genetic disorders are more common than they seem, but diagnosing them remains a challenge even with advancements in genetics and genomics.
- This Review aims to help non-genetics providers understand genetic testing strategies since these tests are increasingly used across various medical settings.
- It covers common genetic testing methods, challenges in identifying genetic variants, and emphasizes the need for better interpretation of genetic results to address misdiagnosed conditions.
Article Synopsis
- * Researchers developed DiGePred, a machine learning tool that identifies potential gene pairs responsible for digenic diseases using biological data and existing gene pair databases.
- * DiGePred shows high accuracy in identifying digenic gene pairs while minimizing false positives and is available for rapid screening of human gene pairs to help uncover genetic causes for rare diseases.
Article Synopsis
- - There is ongoing debate about the effectiveness and risks of different surgical treatments for neurogenic stress urinary incontinence (N-SUI), with the goal of finding the most effective option that maintains urinary tract function and safety.
- - A systematic review of 32 studies involving 852 patients found that the artificial urinary sphincter (AUS) was the most commonly used treatment, but about one-third of patients required additional surgeries, indicating a potential need for multiple interventions.
- - Overall, the study highlighted that while some treatments, like the pubovaginal sling, showed a high success rate in achieving dryness, most evidence comes from retrospective studies, raising concerns about bias and the reliability of the findings.