PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “clinical genetics database”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed2026

Expanding the Clinical Spectrum of DHX30-Related Neurodevelopmental Disorder: A Case Report and a Scoping Review.

BACKGROUND: Whole exome sequencing (WES) has improved diagnostic rates for neurodevelopmental disorders (NDDs) while introducing challenges in novel variant interpretation. DHX30-related NDD (DHX30-NDD) is a recently described condition with an evolving phenotypic spectrum. OBJECTIVES: To expand the understanding of the DHX30-NDD genotype-phenotype spectrum by integrating a case-based WES interpretation with a scoping review. METHODS: We performed comprehensive genetic analysis (karyotyping, microarray, WES) on a proband with global developmental delay (GDD). A systematic literature search of PubMed/MEDLINE, Scopus and Google Scholar from database inception to April 2026 identified 10 publications including 51 individuals with DHX30-NDD. Clinical and genetic data were extracted to characterize the genotype-phenotype spectrum. RESULTS: The proband presented with GDD and right microtia, harbouring a de novo heterozygous pathogenic DHX30 missense variant (c.1478G > A; p.Arg493His), confirming DHX30-NDD. To our knowledge, this is the first reported individual with DHX30-NDD and microtia. The scoping review confirmed DHX30 variants are formed predominantly de novo and affected both sexes (22 males; 29 females). Hallmark manifestations were motor delay (50/51; 98.0%), GDD/ID (48/49; 98.0%), hypotonia (48/51; 94.1%), feeding difficulties (38/51; 74.5%), ataxia (17/23; 73.9%), abnormal brain imaging (36/49; 73.5%) and absent expressive language (35/48; 72.9%). Digital anomalies (31/51; 60.8%), eye anomalies (28/51; 54.9%), autistic behaviours (24/44; 54.5%), sleep disturbances (26/51; 51.0%), joint hypermobility (25/51; 49.0%), microcephaly (23/51; 45.1%) and ear anomalies (22/51; 43.1%) were also frequent. CONCLUSIONS: This study potentially expands the phenotypic spectrum of DHX30-NDD, highlights the clinical utility of WES for diagnosing GDD and underscores the importance of ongoing WES reanalysis for evolving variant interpretation.

DHX30↗
PubMed2007

Molecular testing for Fragile X Syndrome: lessons learned from 119,232 tests performed in a clinical laboratory.

PURPOSE: To examine the data from over 119,000 Fragile X Syndrome tests and 307 prenatal tests to detect unsuspected findings and obtain clinical data when indicated to optimize genetic counseling. METHODS: A proprietary database containing 119,232 consecutive postnatal and 307 prenatal FXS tests performed between November 2, 1992 and June 1, 2006 was queried. RESULTS: The distribution of normal FMR1 alleles was a bimodal distribution with a major peak at 30 repeats and a minor peak at 21 repeats. Of 59,707 tests performed for males, 1.4% had a fully expanded and methylated FMR1 allele. Of 59,525 tests performed for females, 0.61% had an affected FMR1 allele, and 1.7% had a premutation FMR1 allele for a total carrier frequency of 1.3%. When fetuses inherited an expanded maternal allele, the risk of expansion to a full affected allele was 0%, 5%, 30% and 100% for allele sizes of <50, 50-75, 76-100 and >100 repeats, respectively. CONCLUSIONS: These figures can be used for genetic counseling of patients presenting for carrier detection and prenatal diagnosis for Fragile X Syndrome.

Adult↗
PubMed2026

Exploring the Melanoma and Pancreatic Cancer Phenotype of a Potential CDKN2A Founder Variant, I49T (c.146T>C; p.Ile49Thr), in Individuals of Predominantly Mexican Ancestry.

PURPOSE: Pathogenic/likely pathogenic variants (P/LPVs) in the CDKN2A gene cause an increased risk of melanoma (MEL) and pancreatic cancer (PANC). The CDKN2A variant I49T (c.146T>C), reported to be recurrent in Hispanics, has conflicting pathogenicity classifications at laboratories, affecting clinical care. Multiple genetics clinics collaborated to explore cancers associated with I49T. METHODS: Institutional clinical databases were queried for the CDKN2A variants, I49T, known P/LPVs, and c.-2G>A (a benign variant [BV]), and history of PANC and MEL was abstracted. A combination of statistical tests was used to investigate cancer history associations. RESULTS: Data on 203 individuals, with qualifying CDKN2A variants detected on multigene testing between 2012 and 2023, were analyzed (I49T, n = 101; known CDKN2A P/LPVs, n = 57; BV, n = 45). Those with I49T were 91% less likely to have MEL than known CDKN2A P/LPVs (odd ratio [OR] = 0.089 [95% CI, 0.031 to 0.025]; P < .001) and were also less likely to have PANC (OR = 0.45 [95% CI, 0.14 to 1.41]; P = .17). However, mean age at PANC diagnosis for I49T was 56.0 years, significantly younger than known CDKN2A P/LPVs (&#x3bc; = 71.0 years; P = .026). CONCLUSION: In the largest I49T study to date to our knowledge, MEL was significantly less frequent compared with known CDKN2A P/LPVs. Although a nonsignificant trend was observed for less PANC in I49T than known P/LPVs, individuals with I49T presented with PANC at a significantly younger age than those with known CDKN2A P/LPVs. The presence of I49T in Hispanics of mostly Mexican ancestry supports that it is a founder variant, relevant to understanding cancer risk in a large proportion of Hispanics in the United States.

Humans↗
PubMed2000

[Clinical Genetics Network(Idennet) as a back-up system for clinical management of hereditary tumors].

We, Clinical Genetics Unit, Kyoto University Hospital, have established an internet homepage, Clinical Genetics Network(Idennet)(URL: http:¿www.kuhp.kyoto-u.ac.jp/idennet) to provide various information necessary for genetics clinics. One of the most important contents is the "Online Database of Gene Tests" which provides real time information on gene tests performed at research facilities such as universities and available for outsiders. The point of this database is direct input of information by registered users, making information always updated. 46 gene tests for hereditary tumors have been registered in the "Online Database of Gene Tests". This database will be a useful tool for clinical management of patients and family members with hereditary tumors.

Databases, Factual↗
PubMed2003

A new era for preventive genetic programs in the Arabian Peninsula.

In the Arabian Peninsula, high percentages of consanguineous marriages and the tribal nature of marriages have resulted in high incidence of genetically based disorders. The successful management of these disorders incurs a high financial cost, which is a great burden on the health care system. The practical solution to this problem is through prevention. Prevention of genetic disorders should be the utmost public health concern especially where these disorders are prevalent. Preventive genetics became possible with the advent of biochemical and molecular technologies. Biochemical neonatal screening based on tandem mass spectrometry technology and molecular technologies such as sequencing, DNA microarray and nucleic acid hybridization techniques are steadily being transferred to clinical practice. Preventive genetics could be best achieved through establishment of databases for common genetic disorders, premarital diagnosis, and pre-implantation genetic diagnosis and by genetic counseling. These preventive measures must take into account the social and cultural aspects.

Adult↗
PubMed2001

Familial cancer database: a clinical aide-mémoire.

Cancer is associated with a wide range of hereditary disorders. Recognizing these disorders in cancer patients may be of great importance for the medical management of both patients and their relatives. Conversely, recognizing the fact that cancer may develop in patients already diagnosed with a particular hereditary disorder may be important for the same reason. We have developed a stand-alone interactive computer program, Familial Cancer Database (FaCD), to assist the clinician in making a genetic differential diagnosis in cancer patients as well as in becoming aware of the tumour spectrum associated with a particular hereditary disorder. The program tries to match tumour and non-tumour features observed in patients and their families with any of the more than 300 disorders presently contained in its database and provides a clinical synopsis with literature references for each of these disorders. FaCD is offered free of charge in support of the Familial Cancer and Prevention project of the UICC Cancer Epidemiology and Prevention program. The software is primarily aimed at health care professionals with at least a basic knowledge of clinical cancer genetics, and can be downloaded from the internet at http://facd.uicc.org.

Databases, Factual↗
PubMed2000

Prophylactic antibiotics for cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis are sometimes prescribed antibiotics to take continuously on a prophylactic (preventative) basis. This approach is most commonly used in infants where the objective is to reduce pulmonary infection with Staphylococcus aureus and prevent lung damage. This approach may also be used in older patients. This review evaluates the evidence for the effectiveness of this approach and considers potential adverse effects. OBJECTIVES: To compare continuous oral antibiotic prophylaxis with no prophylaxis (short courses of oral antibiotics given as clinically indicated) in patients with cystic fibrosis. This review considers both the effectiveness of prophylaxis (bacteria isolated from the respiratory tract, requirement for additional antibiotic treatment, lung function, survival) and the adverse effects. SEARCH STRATEGY: The Cochrane Cystic Fibrosis and Genetic Disorders Group clinical trials register was used. This comprises references identified from a comprehensive search of electronic databases, as well as hand searching relevant journals and conference abstracts. Companies manufacturing anti-staphylococcal antibiotics were also approached for unpublished data. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All randomised or pseudo-randomised trials where continuous oral prophylactic antibiotics, given for a period of at least one year, were compared to intermittent antibiotic therapy given "as required." Cystic fibrosis patients of any disease severity were considered. DATA COLLECTION AND ANALYSIS: Trials were assessed for eligibility, methodological quality and data extraction by two reviewers (AS & SW). The following outcomes were assessed: lung function; nutrition (weight standard deviation score); survival; requirement for additional antibiotic treatment; isolates of pathogens from the respiratory tract; occurrence of adverse reactions to prophylactic antibiotics. MAIN RESULTS: Only two studies, totalling 66 patients (over half of whom were infants), were suitable for inclusion in the review. A reduced prevalence of Staphylococcus aureus in the respiratory secretions was seen in children receiving anti-staphylococcal antibiotic prophylaxis, although no effect was seen on other common pathogens. This is associated with a reduced requirement for additional courses of oral antibiotics and fewer hospital admissions in the first two years of life in patients receiving prophylaxis. No effect on infant lung function has been shown after one year of prophylactic treatment. Data are not available on adverse effects of the interventions. As the duration of the studies reviewed has been of two years or less, conclusions cannot be drawn about the long term effects of prophylaxis on acquisition of Pseudomonas aeruginosa and survival. REVIEWER'S CONCLUSIONS: Anti-staphylococcal antibiotic prophylaxis may be of benefit when commenced early in infancy and continued up to two years of age. There is insufficient evidence from this review to say whether use in older children, or adults, or for periods of over two year is beneficial.

Adult↗
PubMed1987

The use of a computerised database for the diagnosis of a rare neurological syndrome.

A database which runs on an office microcomputer is being developed for the diagnosis of genetically determined neurological disorders. At present about 1100 conditions with their clinical features and 3000 references are stored in the database. We discuss a family with 3 sibs affected by a unique neurological disorder and show how the database is used. The 3 sibs, 4, 5 and 10 years old, show the same clinical course characterized by congenital cataracts, microcephaly, hypotonia, mental retardation, pyramidal signs and choreoathetoid movements starting in early childhood. The parents are first cousins of Bangladeshi origin. This condition does not appear in published report and is not listed in the database. It can therefore be concluded that the sibs have a unique autosomal recessive disorder.

Athetosis↗
PubMed2026

Pan-cancer characterization of HMGA1 reveals its oncogenic role in tumor microenvironment and stemness: functional validation in pancreatic cancer migration and invasion.

BACKGROUND: HMGA1 is a chromatin-associated oncogenic factor implicated in tumor progression, epithelial-mesenchymal transition (EMT), stemness, and metastasis. However, its pan-cancer expression and prognostic patterns, epigenetic activation, and relationship with malignant-cell stemness/plasticity and tumor microenvironment (TME) remodeling in pancreatic adenocarcinoma (PAAD) remain incompletely defined. This study aimed to systematically characterize HMGA1 across cancers and clarify its clinical and biological relevance in PAAD. METHODS: Pan-cancer transcriptomic, clinical, genetic, methylation, immune, and stemness data were integrated from multiple public databases. PAAD single-cell RNA sequencing data were analyzed to localize HMGA1 expression, infer malignant-cell pseudotime, calculate a stemness module score, and assess ligand-receptor communication using CellChat. Public HMGA1-knockdown RNA sequencing data were reanalyzed to evaluate transcriptional remodeling. The Cancer Genome Atlas (TCGA)-PAAD expression and methylation data were used to assess TME-remodeling, immune-suppression, stemness/plasticity, cytokine/chemokine, checkpoint, and promoter-methylation features. HMGA1 expression and function were further examined using immunohistochemistry (IHC), quantitative real-time polymerase chain reaction, Western blotting, wound-healing assays, and Transwell migration and invasion assays. RESULTS: HMGA1 was upregulated in most tumor types, and high expression was associated with unfavorable survival in multiple cancers, including PAAD. In PAAD, HMGA1 was enriched in malignant epithelial cells and positively correlated with pseudotime (Spearman's rho =0.594), while the stemness module score increased along pseudotime (rho =0.748). HMGA1-high malignant cells showed markedly stronger CellChat-inferred outgoing communication, predominantly involving extracellular matrix (ECM)-receptor, adhesion-related, and selected immunomodulatory ligand-receptor axes. HMGA1 knockdown was associated with broad remodeling of EMT, TGF-&#x3b2;, Hedgehog, IL6/JAK/STAT3, KRAS, and cancer stem cell/stemness-related programs rather than uniform suppression of these programs. HMGA1 promoter methylation was inversely correlated with HMGA1 expression (rho =-0.633) and the TME-remodeling score (rho =-0.347). HMGA1 was associated with selected mediators, including PPIA, PLAU, ANXA1, LGALS9, TGFB1, CD276, and CD47, but not with a generalized checkpoint-high phenotype. Functionally, HMGA1 knockdown significantly reduced pancreatic cancer (PC) cell migration and invasion. CONCLUSIONS: These findings support an association-based model in which promoter hypomethylation-associated HMGA1 activation is linked to malignant epithelial stemness/plasticity, ECM/adhesion-dominant TME remodeling, selected immunomodulatory programs, and aggressive PAAD phenotypes. Further mechanistic and clinical validation is required before HMGA1 can be used for therapeutic stratification or immunotherapy-response prediction.

HMGA1↗
PubMed2006

Mycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology.

BACKGROUND: The Direct Repeat locus of the Mycobacterium tuberculosis complex (MTC) is a member of the CRISPR (Clustered regularly interspaced short palindromic repeats) sequences family. Spoligotyping is the widely used PCR-based reverse-hybridization blotting technique that assays the genetic diversity of this locus and is useful both for clinical laboratory, molecular epidemiology, evolutionary and population genetics. It is easy, robust, cheap, and produces highly diverse portable numerical results, as the result of the combination of (1) Unique Events Polymorphism (UEP) (2) Insertion-Sequence-mediated genetic recombination. Genetic convergence, although rare, was also previously demonstrated. Three previous international spoligotype databases had partly revealed the global and local geographical structures of MTC bacilli populations, however, there was a need for the release of a new, more representative and extended, international spoligotyping database. RESULTS: The fourth international spoligotyping database, SpolDB4, describes 1939 shared-types (STs) representative of a total of 39,295 strains from 122 countries, which are tentatively classified into 62 clades/lineages using a mixed expert-based and bioinformatical approach. The SpolDB4 update adds 26 new potentially phylogeographically-specific MTC genotype families. It provides a clearer picture of the current MTC genomes diversity as well as on the relationships between the genetic attributes investigated (spoligotypes) and the infra-species classification and evolutionary history of the species. Indeed, an independent Naïve-Bayes mixture-model analysis has validated main of the previous supervised SpolDB3 classification results, confirming the usefulness of both supervised and unsupervised models as an approach to understand MTC population structure. Updated results on the epidemiological status of spoligotypes, as well as genetic prevalence maps on six main lineages are also shown. Our results suggests the existence of fine geographical genetic clines within MTC populations, that could mirror the passed and present Homo sapiens sapiens demographical and mycobacterial co-evolutionary history whose structure could be further reconstructed and modelled, thereby providing a large-scale conceptual framework of the global TB Epidemiologic Network. CONCLUSION: Our results broaden the knowledge of the global phylogeography of the MTC complex. SpolDB4 should be a very useful tool to better define the identity of a given MTC clinical isolate, and to better analyze the links between its current spreading and previous evolutionary history. The building and mining of extended MTC polymorphic genetic databases is in progress.

Computational Biology↗
PubMed2001

Standardized evaluation and documentation of findings in patients with craniosynostosis.

Surgical correction of craniosynostosis is usually performed according to standard procedures. However, a standard for clinical examination and report of findings for patients with craniosynostosis does not exist as yet. To compare findings from different hospitals, a documentation system was developed by a national craniosynostosis group. This system comprises a two-page document, clinical photographs, radiographs, CT scans, anthropometric measurements and molecular genetic findings. Data from craniosynostosis patients collected from participating hospitals are stored in a database, which facilitates online access.The documentation system was developed in cooperation with the group during 3 years since 1996. It was evaluated as being practicable and reliable and enables a comparability of findings reported in different hospitals. Molecular genetic analysis was found to support the investigation of patients with craniosynostosis and should therefore be integrated in the clinical evaluation. Copyright 2001 European Association for Cranio-Maxillofacial Surgery.

Journal Article↗
PubMed2004

Genetic counseling program in familial breast cancer: analysis of its effectiveness, cost and cost-effectiveness ratio.

Women with a family history of breast cancer are at increased risk for developing this neoplasm. Starting surveillance more frequently at a younger age than the general population and the possibility of undergoing genetic testing are options for their medical management. We analyzed the benefits and costs of our clinical program in familial breast cancer (FBC) and carried out a cost-effectiveness analysis of such procedure. The benefits and costs of performing genetic counseling and a screening program in FBC based on 143 high-risk families registered in our database between June 1995 and December 2001 were analyzed. A decision tree was constructed to estimate the survival benefit and cost-effectiveness of the clinical genetic counseling program compared with the strategy of not performing any screening protocol. We estimated that the prevalence of a BRCA mutation in an unaffected relative of our high-risk cohort was 10% and that 53% of the mutations are found in the BRCA1 gene. We assigned a 58.5% lifetime risk of breast cancer for a 30-year-old mutation carrier according to the SEER data. The effectiveness of the screening was obtained from our experience and data for estimating survival were derived from other studies with longer follow-up. We used our local payment data to calculate the costs of the program. A mutation in the BRCA1 or BRCA2 genes was identified in 20% of the probands. Seventy primary breast cancer cases were recorded since the onset of the program. Thirty percent of the tumors were diagnosed through the screening program and 71% of them were lymph node-negative compared to 49% of the tumors diagnosed outside the program (p=0.1). The cost-effectiveness ratio of our FBC genetic counseling and screening program was 4,294 euros per life-year gained. The model was sensitive to the prevalence of mutation carriers, the lifetime risk of breast cancer and the effectiveness of the screening. In our setting and according to our model, this analysis suggests that a program of genetic testing and screening for breast cancer in a high-risk population may be cost-effective. These results need to be confirmed as more effective interventions for cancer prevention and screening are being implemented.

Aged↗
PubMed2003

Incipient CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene. Knowledge of disease expression in young adult NOTCH3 mutation carriers (MCs) is limited. OBJECTIVE: To characterize clinical, neuropsychological, and radiological status in NOTCH3 MCs younger than 35 years. DESIGN: Clinical characterization and blinded survey comparing MCs with non-MCs. SETTING: Referral center. PARTICIPANTS: Individuals younger than 35 years who were at a 50% risk of a NOTCH3 mutation, from our CADASIL database. Thirteen individuals, from 8 families, met the criteria. METHODS: Comprehensive clinical, genetic, neuropsychological, and radiological investigations. Magnetic resonance images were scored according to a standardized white matter hyperintensities rating scale. RESULTS: Six individuals, from 5 families, were MCs. Clinical symptoms consisted of migraine (with aura), stroke, and stroke-like episodes. We did not find evidence for psychiatric disturbances, functional disability, or cognitive dysfunction, compared with non-MCs. Radiologically, a characteristic magnetic resonance imaging lesion pattern emerged for all MCs. This comprised white matter hyperintensities in the anterior temporal lobes, the frontal lobes, and the periventricular frontal caps. CONCLUSIONS: Migraine (with aura) and stroke can present in NOTCH3 MCs younger than 35 years; however, more importantly, physical function and cognition are intact. Possible subtle cognitive dysfunction needs to be assessed in a larger study. White matter hyperintensities on magnetic resonance imaging are characteristic, and are consistently visualized from the age of 21 years and onward. Awareness of the clinical and radiological features of CADASIL in those younger than 35 years should increase early diagnosis and allow for customized counseling of young adults from families with CADASIL.

Adult↗
PubMed1988

Use of computers in dysmorphology.

As a consequence of the increasing power and decreasing cost of digital computers, dysmorphologists have begun to explore a wide variety of computerised applications in clinical genetics. Of considerable interest are developments in the areas of syndrome databases, expert systems, literature searches, image processing, and pattern recognition. Each of these areas is reviewed from the perspective of the underlying computer principles, existing applications, and the potential for future developments. Particular emphasis is placed on the analysis of the tasks performed by the dysmorphologist and the design of appropriate tools to facilitate these tasks. In this context the computer and associated software are considered paradigmatically as tools for the dysmorphologist and should be designed accordingly. Continuing improvements in the ability of computers to manipulate vast amounts of data rapidly makes the development of increasingly powerful tools for the dysmorphologist highly probable.

Computers↗
PubMed1997

Automated detection of hereditary syndromes using data mining.

Computer-based data mining methodology applied to family history clinical data can algorithmically create highly accurate, clinically oriented hereditary disease pattern recognizers. For the example of hereditary colon cancer, the data mining's selection of relevant factors to assess for hereditary colon cancer was statistically significant (P < 0.05). All final recognizer-formulated patterns of hereditary colon cancer were independently confirmed by a clinical expert. Applied to previously analyzed family histories, the recognizer identified the definitive hereditary histories, correctly responded negatively to the putative hereditary histories, and correctly responded negatively to empirically elevated colon cancer risk situations. This capability facilitates patient selection for DNA studies in search of gene mutations. When genetic mutations are included as parameters in a patient database for a genetic disease, the process yields an expert system which characterizes variations in clinical disease presentations in terms of genetic mutations. Such information can greatly improve the efficiency of gene testing.

Adult↗