Dysmorphology at a distance: results of a web-based diagnostic service

Douzgou, Sofia; Clayton‐Smith, Jill; Gardner, Sandra; Day, Richard O.; Griffiths, Peter; Strong, Kimberly A.

doi:10.1038/ejhg.2013.137

Cited by 15 publications

(19 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This tool may address the need stated by Yang et al [2014], "refinement of the coupling between clinical data and molecular interpretation is of particular interest because current methods include considerable expert human involvement and are not readily scalable without further automation." We would like to draw attention to this evolving facial dysmorphology analysis technology, not only in the context of exome analysis, but also pertaining to other potentially scalable approaches such as internet based diagnostic services [Douzgou et al, 2013] and telemedicine. While novel facial dysmorphology analysis technology in no way will replace an expert clinician and a comprehensive clinical evaluation, it may become a useful supplemental tool.…”

Section: Using Facial Dysmorphology Data To Inform Variant Analysismentioning

confidence: 99%

The role of objective facial analysis using FDNA in making diagnoses following whole exome analysis. Report of two patients with mutations in the BAF complex genes

Gripp¹,

Baker²,

Telegrafi³

et al. 2016

American J of Med Genetics Pt A

View full text Add to dashboard Cite

The genetic basis of numerous intellectual disability (ID) syndromes has recently been identified by applying exome analysis on a research or clinical basis. There is significant clinical overlap of biologically related syndromes, as exemplified by Nicolaides-Baraitser (NCBRS) and Coffin-Siris (CSS) syndrome. Both result from mutations affecting the BAF (mSWI/SNF) complex and belong to the growing category of BAFopathies. In addition to the notable clinical overlap between these BAFopathies, heterogeneity exists for patients clinically diagnosed with one of these conditions. We report two teenagers with ID whose molecular diagnosis of a SMARC2A or ARID1B mutation, respectively, was established through clinical exome analysis. Interestingly, using only the information provided in a single clinically obtained facial photograph from each patient, the facial dysmorphology analysis detected similarities to facial patterns associated with NCBRS as the first suggestion for both individuals, followed by CSS as the second highest ranked in the individual with the ARID1B mutation. Had this information been available to the laboratory performing the exome analysis, it could have been utilized during the variant analysis and reporting process, in conjunction with the written summary provided with each test requisition. While the available massive parallel sequencing technology, variant calling and variant interpretation are constantly evolving, clinical information remains critical for this diagnostic process. When trio analysis is not feasible, additional diagnostic tools may become particularly valuable. Facial dysmorphology analysis data may supplement the clinical phenotype summary and provide data independent of the clinician's personal experience and bias. © 2016 Wiley Periodicals, Inc.

show abstract

Section: Using Facial Dysmorphology Data To Inform Variant Analysismentioning

confidence: 99%

The role of objective facial analysis using FDNA in making diagnoses following whole exome analysis. Report of two patients with mutations in the BAF complex genes

Gripp¹,

Baker²,

Telegrafi³

et al. 2016

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

“…The clinical evaluation included medical history interviews, a physical examination, and review of medical records. Clinical information of affected individuals from the first two families had been independently submitted to the web-based Dysmorphology Diagnostic System (DDS) of the DYSCERNE network (a European network of centers of expertise for dysmorphology) (Douzgou et al 2014) Whole exome and BRF1 sequencing…”

Section: Methods Subjectsmentioning

confidence: 99%

BRF1 mutations alter RNA polymerase III–dependent transcription and cause neurodevelopmental anomalies

et al. 2015

View full text Add to dashboard Cite

RNA polymerase III (Pol III) synthesizes tRNAs and other small noncoding RNAs to regulate protein synthesis. Dysregulation of Pol III transcription has been linked to cancer, and germline mutations in genes encoding Pol III subunits or tRNA processing factors cause neurogenetic disorders in humans, such as hypomyelinating leukodystrophies and pontocerebellar hypoplasia. Here we describe an autosomal recessive disorder characterized by cerebellar hypoplasia and intellectual disability, as well as facial dysmorphic features, short stature, microcephaly, and dental anomalies. Whole-exome sequencing revealed biallelic missense alterations of BRF1 in three families. In support of the pathogenic potential of the discovered alleles, suppression or CRISPR-mediated deletion of brf1 in zebrafish embryos recapitulated key neurodevelopmental phenotypes; in vivo complementation showed all four candidate mutations to be pathogenic in an apparent isoform-specific context. BRF1 associates with BDP1 and TBP to form the transcription factor IIIB (TFIIIB), which recruits Pol III to target genes. We show that disease-causing mutations reduce Brf1 occupancy at tRNA target genes in Saccharomyces cerevisiae and impair cell growth. Moreover, BRF1 mutations reduce Pol III-related transcription activity in vitro. Taken together, our data show that BRF1 mutations that reduce protein activity cause neurodevelopmental anomalies, suggesting that BRF1-mediated Pol III transcription is required for normal cerebellar and cognitive development.

show abstract

“…Each individual had undergone a standard genetic assessment and had been reviewed by at least one consultant clinical geneticist. All cases had been evaluated following the standard dysmorphology consultation process as described in the guidelines for submission and on‐line proformas used for DYSCERNE . The total number of the eligible records was 268 as follows: Sixty‐eight cases seen in the Genetics Department of the Institute of Child Health, ‘Aghia Sophia’ Children's Hospital, Athens, Greece, between January 2009 and January 2010. Hundred cases seen in the Genetic Institute of the ‘ Ha'Emek ’ Medical Center, Afula, Israel, between November 2013 and April 2014. Hundred cases seen in the MCGM (United Kingdom Dysmorphology Service, UKDS) between March 2011 and March 2012. …”

Section: Methodsmentioning

confidence: 99%

Dysmorphology services: a snapshot of current practices and a vision for the future

et al. 2015

View full text Add to dashboard Cite

Dysmorphology concerns the recognition and management of rare, multiple anomaly syndromes. Genomic technologies and software for gestalt recognition will re-shape dysmorphology services. In order to reflect on a model of the service in the post-genomic era, we compared the utility of dysmorphology consultations in two Mediterranean cities, Athens, Greece and Afula, Israel (MDS), the Manchester Centre for Genomic Medicine, a UK service with dysmorphology expertise (UKDS) and the DYSCERNE, digital service (DDS). We show that it is more likely that chromosome microarray analysis will be performed if suggested in the UKDS rather than in the MDS; this, most probably reflects the difference of access to genetic testing following funding limitations in the MDS. We also show that in terms of achieved diagnosis, the first visit to a dysmorphology clinic is more significant than a follow-up. We show that a confirmed syndrome diagnosis significantly decreases the requests for other, non-genetic, laboratory investigations. Conversely, it increases the requests for reviews by other specialists and, most significantly (t-test: 8.244), it increases further requests for screening for possible associated complications. This is the first demonstration of the demands, on a health service, following the diagnosis of a dysmorphic condition.

show abstract

Dysmorphology at a distance: results of a web-based diagnostic service

Cited by 15 publications

References 13 publications

The role of objective facial analysis using FDNA in making diagnoses following whole exome analysis. Report of two patients with mutations in the BAF complex genes

The role of objective facial analysis using FDNA in making diagnoses following whole exome analysis. Report of two patients with mutations in the BAF complex genes

BRF1 mutations alter RNA polymerase III–dependent transcription and cause neurodevelopmental anomalies

Dysmorphology services: a snapshot of current practices and a vision for the future

Contact Info

Product

Resources

About