Heidi L Rehm

Brigham and Women's Hospital, Boston, Massachusetts, United States

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Publications (83)732.02 Total impact

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    ABSTRACT: On autopsy, a patient is found to have hypertrophic cardiomyopathy. The patient's family pursues genetic testing that shows a "likely pathogenic" variant for the condition on the basis of a study in an original research publication. Given the dominant inheritance of the condition and the risk of sudden cardiac death, other family members are tested for the genetic variant to determine their risk. Several family members test negative and are told that they are not at risk for hypertrophic cardiomyopathy and sudden cardiac death, and those who test positive are told that they need to be regularly monitored for cardiomyopathy . . .
    New England Journal of Medicine 05/2015; 372(23). DOI:10.1056/NEJMsr1406261 · 54.42 Impact Factor
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    ABSTRACT: Glycosaminoglycans (GAGs) such as chondroitin are ubiquitous disaccharide carbohydrate chains that contribute to the formation and function of proteoglycans at the cell membrane and in the extracellular matrix. Although GAG-modifying enzymes are required for diverse cellular functions, the role of these proteins in human development and disease is less well understood. Here, we describe two sisters out of seven siblings affected by congenital limb malformation and malignant lymphoproliferative disease. Using Whole-Genome Sequencing (WGS), we identified in the proband deletion of a 55 kb region within chromosome 12q23 that encompasses part of CHST11 (encoding chondroitin-4-sulfotransferase 1) and an embedded microRNA (MIR3922). The deletion was homozygous in the proband but not in each of three unaffected siblings. Genotyping data from the 1000 Genomes Project suggest that deletions inclusive of both CHST11 and MIR3922 are rare events. Given that CHST11 deficiency causes severe chondrodysplasia in mice that is similar to human limb malformation, these results underscore the importance of chondroitin modification in normal skeletal development. Our findings also potentially reveal an unexpected role for CHST11 and/or MIR3922 as tumor suppressors whose disruption may contribute to malignant lymphoproliferative disease.
    05/2015; DOI:10.1002/mgg3.152
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    ABSTRACT: Disclaimer: These ACMG Standards and Guidelines were developed primarily as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory services. Adherence to these standards and guidelines is voluntary and does not necessarily assure a successful medical outcome. These Standards and Guidelines should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the clinical laboratory geneticist should apply his or her own professional judgment to the specific circumstances presented by the individual patient or specimen. Clinical laboratory geneticists are encouraged to document in the patient's record the rationale for the use of a particular procedure or test, whether or not it is in conformance with these Standards and Guidelines. They also are advised to take notice of the date any particular guideline was adopted and to consider other relevant medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures.The American College of Medical Genetics and Genomics (ACMG) previously developed guidance for the interpretation of sequence variants.(1) In the past decade, sequencing technology has evolved rapidly with the advent of high-throughput next-generation sequencing. By adopting and leveraging next-generation sequencing, clinical laboratories are now performing an ever-increasing catalogue of genetic testing spanning genotyping, single genes, gene panels, exomes, genomes, transcriptomes, and epigenetic assays for genetic disorders. By virtue of increased complexity, this shift in genetic testing has been accompanied by new challenges in sequence interpretation. In this context the ACMG convened a workgroup in 2013 comprising representatives from the ACMG, the Association for Molecular Pathology (AMP), and the College of American Pathologists to revisit and revise the standards and guidelines for the interpretation of sequence variants. The group consisted of clinical laboratory directors and clinicians. This report represents expert opinion of the workgroup with input from ACMG, AMP, and College of American Pathologists stakeholders. These recommendations primarily apply to the breadth of genetic tests used in clinical laboratories, including genotyping, single genes, panels, exomes, and genomes. This report recommends the use of specific standard terminology-"pathogenic," "likely pathogenic," "uncertain significance," "likely benign," and "benign"-to describe variants identified in genes that cause Mendelian disorders. Moreover, this recommendation describes a process for classifying variants into these five categories based on criteria using typical types of variant evidence (e.g., population data, computational data, functional data, segregation data). Because of the increased complexity of analysis and interpretation of clinical genetic testing described in this report, the ACMG strongly recommends that clinical molecular genetic testing should be performed in a Clinical Laboratory Improvement Amendments-approved laboratory, with results interpreted by a board-certified clinical molecular geneticist or molecular genetic pathologist or the equivalent.Genet Med advance online publication 05 March 2015Genetics in Medicine (2015); doi:10.1038/gim.2015.30.
    Genetics in medicine: official journal of the American College of Medical Genetics 03/2015; 17(5). DOI:10.1038/gim.2015.30 · 6.44 Impact Factor
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    ABSTRACT: Recommendations for laboratories to report incidental findings from genomic tests have stimulated interest in such results. In order to investigate the criteria and processes for assigning the pathogenicity of specific variants and to estimate the frequency of such incidental findings in patients of European and African ancestry, we classified potentially actionable pathogenic single-nucleotide variants (SNVs) in all 4300 European- and 2203 African-ancestry participants sequenced by the NHLBI Exome Sequencing Project (ESP). We considered 112 gene-disease pairs selected by an expert panel as associated with medically actionable genetic disorders that may be undiagnosed in adults. The resulting classifications were compared to classifications from other clinical and research genetic testing laboratories, as well as with in silico pathogenicity scores. Among European-ancestry participants, 30 of 4300 (0.7%) had a pathogenic SNV and six (0.1%) had a disruptive variant that was expected to be pathogenic, whereas 52 (1.2%) had likely pathogenic SNVs. For African-ancestry participants, six of 2203 (0.3%) had a pathogenic SNV and six (0.3%) had an expected pathogenic disruptive variant, whereas 13 (0.6%) had likely pathogenic SNVs. Genomic Evolutionary Rate Profiling mammalian conservation score and the Combined Annotation Dependent Depletion summary score of conservation, substitution, regulation, and other evidence were compared across pathogenicity assignments and appear to have utility in variant classification. This work provides a refined estimate of the burden of adult onset, medically actionable incidental findings expected from exome sequencing, highlights challenges in variant classification, and demonstrates the need for a better curated variant interpretation knowledge base. © 2015 Amendola et al.; Published by Cold Spring Harbor Laboratory Press.
    Genome Research 01/2015; 25(3). DOI:10.1101/gr.183483.114 · 13.85 Impact Factor
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    ABSTRACT: Purpose:Hypertrophic cardiomyopathy (HCM) is caused primarily by pathogenic variants in genes encoding sarcomere proteins. We report genetic testing results for HCM in 2,912 unrelated individuals with nonsyndromic presentations from a broad referral population over 10 years.Methods:Genetic testing was performed by Sanger sequencing for 10 genes from 2004 to 2007, by HCM CardioChip for 11 genes from 2007 to 2011 and by next-generation sequencing for 18, 46, or 51 genes from 2011 onward.Results:The detection rate is ~32% among unselected probands, with inconclusive results in an additional 15%. Detection rates were not significantly different between adult and pediatric probands but were higher in females compared with males. An expanded gene panel encompassing more than 50 genes identified only a very small number of additional pathogenic variants beyond those identifiable in our original panels, which examined 11 genes. Familial genetic testing in at-risk family members eliminated the need for longitudinal cardiac evaluations in 691 individuals. Based on the projected costs derived from Medicare fee schedules for the recommended clinical evaluations of HCM family members by the American College of Cardiology Foundation/American Heart Association, our data indicate that genetic testing resulted in a minimum cost savings of about $0.7 million.Conclusion:Clinical HCM genetic testing provides a definitive molecular diagnosis for many patients and provides cost savings to families. Expanded gene panels have not substantively increased the clinical sensitivity of HCM testing, suggesting major additional causes of HCM still remain to be identified.Genet Med advance online publication 22 January 2015Genetics in Medicine (2015); doi:10.1038/gim.2014.205.
    Genetics in medicine: official journal of the American College of Medical Genetics 01/2015; DOI:10.1038/gim.2014.205 · 6.44 Impact Factor
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    ABSTRACT: As genome sequencing technologies increasingly enter medical practice, genetics laboratories must communicate sequencing results effectively to nongeneticist physicians. We describe the design and delivery of a clinical genome sequencing report, including a one-page summary suitable for interpretation by primary care physicians. To illustrate our preliminary experience with this report, we summarize the genomic findings from 10 healthy participants in a study of genome sequencing in primary care. © 2015 S. Karger AG, Basel.
    Public Health Genomics 01/2015; 18(2). DOI:10.1159/000370102 · 2.46 Impact Factor
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    ABSTRACT: Success rates for genomic analyses of highly heterogeneous disorders can be greatly improved if a large cohort of patient data is assembled to enhance collective capabilities for accurate sequence variant annotation, analysis, and interpretation. Indeed, molecular diagnostics requires the establishment of robust data resources to enable data sharing that informs accurate understanding of genes, variants, and phenotypes. The "Mitochondrial Disease Sequence Data Resource (MSeqDR) Consortium" is a grass-roots effort facilitated by the United Mitochondrial Disease Foundation to identify and prioritize specific genomic data analysis needs of the global mitochondrial disease clinical and research community. A central Web portal (https://mseqdr.org) facilitates the coherent compilation, organization, annotation, and analysis of sequence data from both nuclear and mitochondrial genomes of individuals and families with suspected mitochondrial disease. This Web portal provides users with a flexible and expandable suite of resources to enable variant-, gene-, and exome-level sequence analysis in a secure, Web-based, and user-friendly fashion. Users can also elect to share data with other MSeqDR Consortium members, or even the general public, either by custom annotation tracks or through the use of a convenient distributed annotation system (DAS) mechanism. A range of data visualization and analysis tools are provided to facilitate user interrogation and understanding of genomic, and ultimately phenotypic, data of relevance to mitochondrial biology and disease. Currently available tools for nuclear and mitochondrial gene analyses include an MSeqDR GBrowse instance that hosts optimized mitochondrial disease and mitochondrial DNA (mtDNA) specific annotation tracks, as well as an MSeqDR locus-specific database (LSDB) that curates variant data on more than 1300 genes that have been implicated in mitochondrial disease and/or encode mitochondria-localized proteins. MSeqDR is integrated with a diverse array of mtDNA data analysis tools that are both freestanding and incorporated into an online exome-level dataset curation and analysis resource (GEM.app) that is being optimized to support needs of the MSeqDR community. In addition, MSeqDR supports mitochondrial disease phenotyping and ontology tools, and provides variant pathogenicity assessment features that enable community review, feedback, and integration with the public ClinVar variant annotation resource. A centralized Web-based informed consent process is being developed, with implementation of a Global Unique Identifier (GUID) system to integrate data deposited on a given individual from different sources. Community-based data deposition into MSeqDR has already begun. Future efforts will enhance capabilities to incorporate phenotypic data that enhance genomic data analyses. MSeqDR will fill the existing void in bioinformatics tools and centralized knowledge that are necessary to enable efficient nuclear and mtDNA genomic data interpretation by a range of shareholders across both clinical diagnostic and research settings. Ultimately, MSeqDR is focused on empowering the global mitochondrial disease community to better define and explore mitochondrial diseases. Copyright © 2014 Elsevier Inc. All rights reserved.
    Molecular Genetics and Metabolism 12/2014; DOI:10.1016/j.ymgme.2014.11.016 · 2.83 Impact Factor
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    ABSTRACT: The MedSeq Project is a randomized clinical trial developing approaches to assess the impact of integrating genome sequencing into clinical medicine. To facilitate the return of results of potential medical relevance to physicians and patients participating in the MedSeq Project, we sought to develop a reporting approach for the effective communication of such findings. Genome sequencing was performed on the Illumina HiSeq platform. Variants were filtered, interpreted, and validated according to methods developed by the Laboratory for Molecular Medicine and consistent with current professional guidelines. The GeneInsight software suite, which is integrated with the Partners HealthCare electronic health record, was used for variant curation, report drafting, and delivery. We developed a concise 5-6 page Genome Report (GR) featuring a single-page summary of results of potential medical relevance with additional pages containing structured variant, gene, and disease information along with supporting evidence for reported variants and brief descriptions of associated diseases and clinical implications. The GR is formatted to provide a succinct summary of genomic findings, enabling physicians to take appropriate steps for disease diagnosis, prevention, and management in their patients. Our experience highlights important considerations for the reporting of results of potential medical relevance and provides a framework for interpretation and reporting practices in clinical genome sequencing.
    BMC Medical Genetics 12/2014; 15(1). DOI:10.1186/s12881-014-0134-1 · 2.45 Impact Factor
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    ABSTRACT: Purpose:Disease-causing mutations and pharmacogenomic variants are of primary interest for clinical whole-genome sequencing. However, estimating genetic liability for common complex diseases using established risk alleles might one day prove clinically useful.Methods:We compared polygenic scoring methods using a case-control data set with independently discovered risk alleles in the MedSeq Project. For eight traits of clinical relevance in both the primary-care and cardiomyopathy study cohorts, we estimated multiplicative polygenic risk scores using 161 published risk alleles and then normalized them using the population median estimated from the 1000 Genomes Project.Results:Our polygenic score approach identified the overrepresentation of independently discovered risk alleles in cases as compared with controls using a large-scale genome-wide association study data set. In addition to normalized multiplicative polygenic risk scores and rank in a population, the disease prevalence and proportion of heritability explained by known common risk variants provide important context in the interpretation of modern multilocus disease risk models.Conclusion:Our approach in the MedSeq Project demonstrates how complex trait risk variants from an individual genome can be summarized and reported for the general clinician and also highlights the need for definitive clinical studies to obtain reference data for such estimates and to establish clinical utility.Genet Med advance online publication 23 October 2014Genetics in Medicine (2014); doi:10.1038/gim.2014.143.
    Genetics in medicine: official journal of the American College of Medical Genetics 10/2014; DOI:10.1038/gim.2014.143 · 6.44 Impact Factor
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    ABSTRACT: Next-generation sequencing (NGS) technologies have revolutionized genetic testing by enabling simultaneous analysis of unprecedented numbers of genes. However, genes with high-sequence homology pose challenges to current NGS technologies. Because diagnostic sequencing is moving toward exome analysis, knowledge of these homologous genes is essential to avoid false positive and negative results. An example is the STRC gene, one of >70 genes known to contribute to the genetic basis of hearing loss. STRC is 99.6% identical to a pseudogene (pSTRC) and therefore inaccessible to standard NGS methodologies. The STRC locus is also known to be a common site for large deletions. Comprehensive diagnostic testing for inherited hearing loss therefore necessitates a combination of several approaches to avoid pseudogene interference. We have developed a clinical test that combines standard NGS and NGS-based copy number assessment supplemented with a long-range PCR-based Sanger or MiSeq assay to eliminate pseudogene contamination. By using this combination of assays we could identify biallelic STRC variants in 14% (95% CI, 8%-24%) of persons with isolated nonsyndromic hearing loss who had previously tested negative on our 70-gene hearing loss panel, corresponding to a detection rate of 11.2% (95% CI, 6%-19%) for previously untested patients. This approach has broad applicability because medically significant genes for many disease areas include genes with high-sequence homology.
    The Journal of molecular diagnostics: JMD 08/2014; 16(6). DOI:10.1016/j.jmoldx.2014.06.003 · 3.96 Impact Factor
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    ABSTRACT: As more research studies incorporate next-generation sequencing (including whole-genome or whole-exome sequencing), investigators and institutional review boards face difficult questions regarding which genomic results to return to research participants and how. An American College of Medical Genetics and Genomics 2013 policy paper suggesting that pathogenic mutations in 56 specified genes should be returned in the clinical setting has raised the question of whether comparable recommendations should be considered in research settings. The Clinical Sequencing Exploratory Research (CSER) Consortium and the Electronic Medical Records and Genomics (eMERGE) Network are multisite research programs that aim to develop practical strategies for addressing questions concerning the return of results in genomic research. CSER and eMERGE committees have identified areas of consensus regarding the return of genomic results to research participants. In most circumstances, if results meet an actionability threshold for return and the research participant has consented to return, genomic results, along with referral for appropriate clinical follow-up, should be offered to participants. However, participants have a right to decline the receipt of genomic results, even when doing so might be viewed as a threat to the participants' health. Research investigators should be prepared to return research results and incidental findings discovered in the course of their research and meeting an actionability threshold, but they have no ethical obligation to actively search for such results. These positions are consistent with the recognition that clinical research is distinct from medical care in both its aims and its guiding moral principles.
    The American Journal of Human Genetics 05/2014; DOI:10.1016/j.ajhg.2014.04.009 · 10.99 Impact Factor
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    ABSTRACT: The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development.
    Nature 04/2014; 508(7497):469-76. DOI:10.1038/nature13127 · 42.35 Impact Factor
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    ABSTRACT: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data was donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
    Genome biology 03/2014; 15(3):R53. DOI:10.1186/gb-2014-15-3-r53 · 10.47 Impact Factor
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    ABSTRACT: Whole genome sequencing (WGS) is already being used in certain clinical and research settings, but its impact on patient well-being, health-care utilization, and clinical decision-making remains largely unstudied. It is also unknown how best to communicate sequencing results to physicians and patients to improve health. We describe the design of the MedSeq Project: the first randomized trials of WGS in clinical care.Methods/design: This pair of randomized controlled trials compares WGS to standard of care in two clinical contexts: (a) disease-specific genomic medicine in a cardiomyopathy clinic and (b) general genomic medicine in primary care. We are recruiting 8 to 12 cardiologists, 8 to 12 primary care physicians, and approximately 200 of their patients. Patient participants in both the cardiology and primary care trials are randomly assigned to receive a family history assessment with or without WGS. Our laboratory delivers a genome report to physician participants that balances the needs to enhance understandability of genomic information and to convey its complexity. We provide an educational curriculum for physician participants and offer them a hotline to genetics professionals for guidance in interpreting and managing their patients' genome reports. Using varied data sources, including surveys, semi-structured interviews, and review of clinical data, we measure the attitudes and behaviors of physician and patient participants at multiple time points before and after the disclosure of these results. The impact of emerging sequencing technologies on patient care is unclear. We have designed a process of interpreting WGS results and delivering them to physicians in a way that anticipates how we envision genomic medicine to evolve in the near future. That is, our WGS report provides clinically relevant information while communicating the complexity and uncertainty of WGS results to physicians and, through physicians, to their patients. This project will not only illuminate the impact of integrating genomic medicine into the clinical care of patients but also inform the design of future studies.Trial registration: ClinicalTrials.gov identifier NCT01736566.
    Trials 03/2014; 15(1):85. DOI:10.1186/1745-6215-15-85 · 2.12 Impact Factor
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    ABSTRACT: Hearing loss is a common and complex condition that can occur at any age, can be inherited or acquired, and is associated with a remarkably wide array of etiologies. The diverse causes of hearing loss, combined with the highly variable and often overlapping presentations of different forms of hearing loss, challenge the ability of traditional clinical evaluations to arrive at an etiologic diagnosis for many deaf and hard-of-hearing individuals. However, identifying the etiology of a hearing loss may affect clinical management, improve prognostic accuracy, and refine genetic counseling and assessment of the likelihood of recurrence for relatives of deaf and hard-of-hearing individuals. Linguistic and cultural identities associated with being deaf or hard of hearing can complicate access to and the effectiveness of clinical care. These concerns can be minimized when genetic and other health-care services are provided in a linguistically and culturally sensitive manner. This guideline offers information about the frequency, causes, and presentations of hearing loss and suggests approaches to the clinical evaluation of deaf and hard-of-hearing individuals aimed at identifying an etiologic diagnosis and providing informative and effective patient education and genetic counseling.Genet Med advance online publication 20 March 2014Genetics in Medicine (2014); doi:10.1038/gim.2014.2.
    Genetics in medicine: official journal of the American College of Medical Genetics 03/2014; DOI:10.1038/gim.2014.2 · 6.44 Impact Factor
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    ABSTRACT: Purpose:Dilated cardiomyopathy is characterized by substantial locus, allelic, and clinical heterogeneity that necessitates testing of many genes across clinically overlapping diseases. Few studies have sequenced sufficient individuals; thus, the contributions of individual genes and the pathogenic variant spectrum are still poorly defined. We analyzed 766 dilated cardiomyopathy patients tested over 5 years in our molecular diagnostics laboratory.Methods:Patients were tested using gene panels of increasing size from 5 to 46 genes, including 121 cases tested with a multiple-cardiomyopathy next-generation panel covering 46 genes. All variants were reassessed using our current clinical-grade scoring system to eliminate false-positive disease associations that afflict many older analyses.Results:Up to 37% of dilated cardiomyopathy cases carry a clinically relevant variant in one of 20 genes, titin (TTN) being the largest contributor (up to 14%). Desmoplakin (DSP), an arrhythmogenic right ventricular cardiomyopathy gene, contributed 2.4%, illustrating the utility of multidisease testing. The clinical sensitivity increased from 10 to 37% as gene panel sizes increased. However, the number of inconclusive cases also increased from 4.6 to 51%.Conclusion:Our data illustrate the utility of broad gene panels for genetically and clinically heterogeneous diseases but also highlight challenges as molecular diagnostics moves toward genome-wide testing.Genet Med advance online publication 6 February 2014Genetics in Medicine (2014); doi:10.1038/gim.2013.204.
    Genetics in medicine: official journal of the American College of Medical Genetics 02/2014; 16(8). DOI:10.1038/gim.2013.204 · 6.44 Impact Factor
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    ABSTRACT: Variants in the head and tail domains of the MYO7A gene, encoding myosin VIIA, cause Usher syndrome type 1B (USH1B) and nonsyndromic deafness (DFNB2, DFNA11). In order to identify the genetic defect(s) underling profound deafness in two consanguineous Arab families living in UAE, we have sequenced a panel of 19 genes involved in Usher syndrome and nonsyndromic deafness in the index cases of the two families. This analysis revealed a novel homozygous insertion of AG (c.1952_1953insAG/p.C652fsX11) in exon 17 of the MYO7A gene in an Iraqi family, and a homozygous point mutation (c.5660C>T/p.P1887L) in exon 41 affecting the same gene in a large Palestinian family. Moreover, some individuals from the Palestinian family also harbored a novel heterozygous truncating variant (c.1267C>T/p.R423X) in the DFNB31 gene, which is involved in autosomal recessive nonsyndromic deafness type DFNB31 and Usher syndrome type II. Assuming an autosomal recessive mode of inheritance in the two inbred families, we conclude that the homozygous variants in the MYO7A gene are the disease-causing mutations in these families. Furthermore, given the absence of retinal disease in all affected patients examined, particularly a 28 year old patient, suggests that at least one family may segregate a DFNB2 presentation rather than USH1B. This finding further supports the premise that the MYO7A gene is responsible for two distinct diseases and gives evidence that the p.P1887L mutation in a homozygous state may be responsible for nonsyndromic hearing loss.
    Molecular Biology Reports 11/2013; 41(1). DOI:10.1007/s11033-013-2851-5 · 1.96 Impact Factor

Publication Stats

2k Citations
732.02 Total Impact Points

Institutions

  • 2009–2015
    • Brigham and Women's Hospital
      • Department of Pathology
      Boston, Massachusetts, United States
    • Abbott Northwestern Hospital
      Minneapolis, Minnesota, United States
  • 1997–2015
    • Harvard Medical School
      • • Department of Pathology
      • • Department of Otology and Laryngology
      • • Department of Genetics
      Boston, Massachusetts, United States
  • 2014
    • Partners HealthCare
      Boston, Massachusetts, United States
  • 2003–2014
    • Harvard University
      Cambridge, Massachusetts, United States
  • 2013
    • University of Alabama at Birmingham
      • Department of Genetics
      Birmingham, AL, United States
  • 2007–2012
    • Boston Children's Hospital
      • Department of Pathology
      Boston, Massachusetts, United States
  • 2011
    • Massachusetts General Hospital
      Boston, Massachusetts, United States