Publications by authors named "Devon Lamb-Thrush"

17 Publications

  • Page 1 of 1

Facing the challenge of genetic counselors' need for rapid continuing education about genomic technologies.

J Genet Couns 2020 10 9;29(5):838-848. Epub 2020 Jan 9.

Department of Medical Affairs, Guardant Health, Redwood City, CA, USA.

The last couple of decades have seen the rapid advancement of genomic technologies (GT) and their equally rapid adoption into clinical testing. Regardless of specialty, all genetic counselors are unified by the fundamental goal to aid in diagnosing patient's genetic disease underscoring the importance for genetic counselors to maintain an in-depth understanding of GT. The National Society of Genetic Counselors' (NSGC) GT Special Interest Group conducted an online survey of NSGC members to assess current genomic technologies knowledge gaps. A total of 171 individuals from a variety of primary work settings completed the survey sufficiently to be included in the analysis. The majority of respondents received their degree in genetic counseling in more recent years (2000-2015). On average across all technologies, >70% of respondents deemed knowledge of GTs as important for successful job performance, 55% responded that additional job training in GTs is needed to successfully perform job functions, and only 28% responded that graduate training in GTs was good. Overall, the data show that participating genetic counselors perceive that their knowledge of GTs is inadequate while it is a key component of their jobs. These results have implications both for training programs and for continuing education efforts. These data can be used as a starting point for additional research into GT educational needs of genetic counselors.
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http://dx.doi.org/10.1002/jgc4.1213DOI Listing
October 2020

Clinical validity assessment of genes for inclusion in multi-gene panel testing: A systematic approach.

Mol Genet Genomic Med 2019 05 21;7(5):e630. Epub 2019 Mar 21.

Ambry Genetics, Aliso Viejo, California.

Background: Advances in sequencing technology have led to expanded use of multi-gene panel tests (MGPTs) for clinical diagnostics. Well-designed MGPTs must balance increased detection of clinically significant findings while mitigating the increase in variants of uncertain significance (VUS). To maximize clinical utililty, design of such panels should include comprehensive gene vetting using a standardized clinical validity (CV) scoring system.

Methods: To assess the impact of CV-based gene vetting on MGPT results, data from MGPTs for cardiovascular indications were retrospectively analyzed. Using our CV scoring system, genes were categorized as having definitive, strong, moderate, or limited evidence. The rates of reported pathogenic or likely pathogenic variants and VUS were then determined for each CV category.

Results: Of 106 total genes, 42% had definitive, 17% had strong, 29% had moderate, and 12% had limited CV. The detection rate of variants classified as pathogenic or likely pathogenic was higher for genes with greater CV, while the VUS rate showed an inverse relationship with CV score. No pathogenic or likely pathogenic findings were observed in genes with a limited CV.

Conclusion: These results demonstrate the importance of a standardized, evidence-based vetting process to establish CV for genes on MGPTs. Using our proposed system may help to increase the detection rate while mitigating higher VUS rates.
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http://dx.doi.org/10.1002/mgg3.630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6503028PMC
May 2019

Pericentromeric regions of homozygosity on the X chromosome: Another likely benign population variant.

Eur J Med Genet 2018 Jul 20;61(7):416-420. Epub 2018 Mar 20.

The Institute for Genomic Medicine at Nationwide Children's Hospital, Columbus, OH, USA; The Ohio State University College of Medicine, Department of Pathology, Columbus, OH, USA. Electronic address:

Purpose: While chromosomal regions of homozygosity (ROH) may implicate genes in known recessive disorders, their correlation to disease pathogenicity remains unclear. ROH around the centromere of the X chromosome (pericentromeric, pROH) is regarded as benign, although this has not been empirically demonstrated.

Methods: We examined microarray results from 122 female individuals harboring ROH bordering the X centromere.

Results: Consecutive ROH was most frequently observed for regions Xp11.23 to Xp11.21 and Xq11.1 to Xq12, with an average total size of 16.5 Mb. X chromosome pROH was unlikely related to phenotype in 41% (50/122) of cases due to other explanations: likely pathogenic deletion/duplication (17%, 21/122), apparently unaffected female (7%, 8/122), other clinical explanation (7%, 9/122), or consanguinity (10%, 12/122). Of the remaining cases with pROH as the only finding, four genes were associated with recessive disorders that overlapped one or more clinical features reported in our probands (KDM5C, FGD1, ZC4H2, and LAS1L). X chromosome pROH observed in our cohort overlapped with previously reported regions.

Conclusions: pROH on the X chromosome are commonly observed in both affected individuals with alternate causes of disease as well as in unaffected individuals, suggesting that X chromosome pROH has no clinically significant effect on phenotype.
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http://dx.doi.org/10.1016/j.ejmg.2018.02.008DOI Listing
July 2018

Variability in pathogenicity prediction programs: impact on clinical diagnostics.

Mol Genet Genomic Med 2015 Mar 3;3(2):99-110. Epub 2014 Dec 3.

Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital Columbus, Ohio ; Department of Pathology, The Ohio State University College of Medicine Columbus, Ohio.

Current practice by clinical diagnostic laboratories is to utilize online prediction programs to help determine the significance of novel variants in a given gene sequence. However, these programs vary widely in their methods and ability to correctly predict the pathogenicity of a given sequence change. The performance of 17 publicly available pathogenicity prediction programs was assayed using a dataset consisting of 122 credibly pathogenic and benign variants in genes associated with the RASopathy family of disorders and limb-girdle muscular dystrophy. Performance metrics were compared between the programs to determine the most accurate program for loss-of-function and gain-of-function mechanisms. No one program correctly predicted the pathogenicity of all variants analyzed. A major hindrance to the analysis was the lack of output from a significant portion of the programs. The best performer was MutPred, which had a weighted accuracy of 82.6% in the full dataset. Surprisingly, combining the results of the top three programs did not increase the ability to predict pathogenicity over the top performer alone. As the increasing number of sequence changes in larger datasets will require interpretation, the current study demonstrates that extreme caution must be taken when reporting pathogenicity based on statistical online protein prediction programs in the absence of functional studies.
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http://dx.doi.org/10.1002/mgg3.116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367082PMC
March 2015

Atypical breakpoint in a t(6;17) translocation case of acampomelic campomelic dysplasia.

Eur J Med Genet 2014 Jul 10;57(7):315-8. Epub 2014 May 10.

Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA; Department of Pathology, The Ohio State University College of Medicine, Columbus, OH, USA. Electronic address:

Campomelic dysplasia (CD) is a skeletal dysplasia characterized by Pierre Robin sequence (PRS), shortened and bowed long bones, airway instability, and the potential for sex reversal. A subtype of CD, acampomelic CD (ACD), is seen in approximately 10% of cases and preserves long bone straightness. Both syndromes are caused by alterations in SOX9, with translocations and missense mutations being overrepresented in ACD cases. We report a term infant with PRS, severe cervical spine abnormalities, eleven rib pairs, hypoplastic scapulae, and female genitalia. Chromosome analysis identified a 46,XY,t(6;17)(q25;q24) karyotype. FISH analysis with a series of BAC probes localized the translocation breakpoints to 6q27 and a region at 17q24.3 in the range of 459-379 kb upstream of SOX9. Therefore, this case extends the region classified as the proximal breakpoint cluster. In addition, the comorbidity of acampomelia, complete sex reversal, and severe spinal anomalies in our patient underscores the variability in the level of malformation in the CD/ACD family of disorders.
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http://dx.doi.org/10.1016/j.ejmg.2014.04.018DOI Listing
July 2014

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge.

Genome Biol 2014 Mar 25;15(3):R53. Epub 2014 Mar 25.

Background: 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 were 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.1186/gb-2014-15-3-r53DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4073084PMC
March 2014

Autosomal dominant pseudohypoaldosteronism type 1 in an infant with salt wasting crisis associated with urinary tract infection and obstructive uropathy.

Case Rep Endocrinol 2013 19;2013:524647. Epub 2013 Dec 19.

Division of Neonatology, Nationwide Children's Hospital/The Ohio State University College of Medicine, Columbus, OH 43205, USA.

Type 1 pseudohypoaldosteronism (PHA1) is a salt wasting syndrome caused by renal resistance to aldosterone. Primary renal PHA1 or autosomal dominant PHA1 is caused by mutations in mineralocorticoids receptor gene (NR3C2), while secondary PHA1 is frequently associated with urinary tract infection (UTI) and/or urinary tract malformations (UTM). We report a 14-day-old male infant presenting with severe hyperkalemia, hyponatremic dehydration, metabolic acidosis, and markedly elevated serum aldosterone level, initially thought to have secondary PHA1 due to the associated UTI and posterior urethral valves. His serum aldosterone remained elevated at 5 months of age, despite resolution of salt wasting symptoms. Chromosomal microarray analysis revealed a deletion of exons 3-5 in NR3C2 in the patient and his asymptomatic mother who also had elevated serum aldosterone level, confirming that he had primary or autosomal dominant PHA1. Our case raises the possibility that some patients with secondary PHA1 attributed to UTI and/or UTM may instead have primary autosomal dominant PHA1, for which genetic testing should be considered to identify the cause, determine future recurrence risk, and possibly prevent the life-threatening salt wasting in a subsequent family member. Future clinical research is needed to investigate the potential overlapping between secondary PHA1 and primary autosomal dominant PHA1.
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http://dx.doi.org/10.1155/2013/524647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3880733PMC
January 2014

MCPH1 deletion in a newborn with severe microcephaly and premature chromosome condensation.

Eur J Med Genet 2013 Nov 27;56(11):609-13. Epub 2013 Sep 27.

Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA.

A newborn with severe microcephaly and a history of parental consanguinity was referred for cytogenetic analysis and subsequently for genetic evaluation. While a 46,XY karyotype was eventually obtained, premature chromosome condensation was observed. A head MRI confirmed primary microcephaly. This combination of features focused clinical interest on the MCPH1 gene and directed genetic testing by sequence analysis and duplication/deletion studies disclosed a homozygous deletion of exons 1-11 of the MCPH1 gene. This case illustrates a strength of standard cytogenetic evaluation in directing molecular testing to a single target gene in this disorder, allowing much more rapid diagnosis at a substantial cost savings for this family.
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http://dx.doi.org/10.1016/j.ejmg.2013.09.007DOI Listing
November 2013

Characterization of copy number variation in genomic regions containing STR loci using array comparative genomic hybridization.

Forensic Sci Int Genet 2013 Sep 28;7(5):475-81. Epub 2013 Jun 28.

Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA.

Short tandem repeat (STR) loci are commonly used in forensic casework, familial analysis for human identification, and for monitoring hematopoietic cell engraftment after bone marrow transplant. Unexpected genetic variation leading to sequence and length differences in STR loci can complicate STR typing, and presents challenges in casework interpretation. Copy number variation (CNV) is a relatively recently identified form of genetic variation consisting of genomic regions present at variable copy numbers within an individual compared to a reference genome. Large scale population studies have demonstrated that likely all individuals carry multiple regions with CNV of 1kb in size or greater in their genome. To date, no study correlating genomic regions containing STR loci with CNV has been conducted. In this study, we analyzed results from 32,850 samples sent for clinical array comparative genomic hybridization (CGH) analysis for the presence of CNV at regions containing the 13 CODIS (Combined DNA Index System) STR, and the Amelogenin X (AMELX) and Amelogenin Y (AMELY) loci. Thirty-two individuals with CNV involving STR loci on chromosomes 2, 4, 7, 11, 12, 13, 16, and 21, and twelve with CNV involving the AMELX/AMELY loci were identified. These results were correlated with data from publicly available databases housing information on CNV identified in normal populations and additional clinical cases. These collective results demonstrate the presence of CNV in regions containing 9 of the 13 CODIS STR and AMELX/Y loci. Further characterization of STR profiles within regions of CNV, additional cataloging of these variants in multiple populations, and contributing such examples to the public domain will provide valuable information for reliable use of these loci.
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http://dx.doi.org/10.1016/j.fsigen.2013.05.008DOI Listing
September 2013

Multigeneration family with short stature, developmental delay, and dysmorphic features due to 4q27-q28.1 microdeletion.

Eur J Med Genet 2013 Sep 26;56(9):521-5. Epub 2013 Jul 26.

Department of Pediatrics, The Ohio State University College of Medicine, Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA. Electronic address:

Deletions of the long arm of chromosome 4 are rare but have been previously reported to be associated with craniofacial anomalies, digital anomalies, developmental delay, growth failure, and cardiovascular anomalies. Strehle et al. previously presented 20 patients with 4q deletions and began to construct a phenotype-genotype map for chromosome 4q. This report follows up on that work by providing clinical and molecular cytogenetic data on a three generation pedigree including seven patients with short stature, dysmorphic features, and developmental delay identified to have a 4q27-q28.1 microdeletion of approximately 5.68 Mb by oligonucleotide chromosomal microarray. This family represents a rare report of an inherited interstitial deletion of the long arm of chromosome 4. To our knowledge, only two cases have been previously reported. The contribution of candidate genes in the region is discussed.
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http://dx.doi.org/10.1016/j.ejmg.2013.07.004DOI Listing
September 2013

A case of an atypically large proximal 15q deletion as cause for Prader-Willi syndrome arising from a de novo unbalanced translocation.

Eur J Med Genet 2013 Sep 13;56(9):510-4. Epub 2013 Jul 13.

Department of Pediatrics, The Ohio State University College of Medicine, Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA. Electronic address:

We describe an 11 month old female with Prader-Willi syndrome (PWS) resulting from an atypically large deletion of proximal 15q due to a de novo 3;15 unbalanced translocation. The 10.6 Mb deletion extends from the chromosome 15 short arm and is not situated in a region previously reported as a common distal breakpoint for unbalanced translocations. There was no deletion of the reciprocal chromosome 3q subtelomeric region detected by either chromosomal microarray or FISH. The patient has hypotonia, failure to thrive, and typical dysmorphic facial features for PWS. The patient also has profound global developmental delay consistent with an expanded, more severe, phenotype.
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http://dx.doi.org/10.1016/j.ejmg.2013.05.010DOI Listing
September 2013

Exonic deletions in AUTS2 cause a syndromic form of intellectual disability and suggest a critical role for the C terminus.

Am J Hum Genet 2013 Feb 17;92(2):210-20. Epub 2013 Jan 17.

Department of Clinical Genetics, VU University Medical Center, Amsterdam 1007 MB, The Netherlands.

Genomic rearrangements involving AUTS2 (7q11.22) are associated with autism and intellectual disability (ID), although evidence for causality is limited. By combining the results of diagnostic testing of 49,684 individuals, we identified 24 microdeletions that affect at least one exon of AUTS2, as well as one translocation and one inversion each with a breakpoint within the AUTS2 locus. Comparison of 17 well-characterized individuals enabled identification of a variable syndromic phenotype including ID, autism, short stature, microcephaly, cerebral palsy, and facial dysmorphisms. The dysmorphic features were more pronounced in persons with 3'AUTS2 deletions. This part of the gene is shown to encode a C-terminal isoform (with an alternative transcription start site) expressed in the human brain. Consistent with our genetic data, suppression of auts2 in zebrafish embryos caused microcephaly that could be rescued by either the full-length or the C-terminal isoform of AUTS2. Our observations demonstrate a causal role of AUTS2 in neurocognitive disorders, establish a hitherto unappreciated syndromic phenotype at this locus, and show how transcriptional complexity can underpin human pathology. The zebrafish model provides a valuable tool for investigating the etiology of AUTS2 syndrome and facilitating gene-function analysis in the future.
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http://dx.doi.org/10.1016/j.ajhg.2012.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3567268PMC
February 2013

12q14 microdeletion associated with HMGA2 gene disruption and growth restriction.

Am J Med Genet A 2012 Nov 14;158A(11):2925-30. Epub 2012 Sep 14.

Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, Ohio 43205, USA.

The 12q14 microdeletion syndrome is a rare condition that has previously been characterized by pre- and postnatal growth restriction, proportionate short stature, failure to thrive, developmental delay, and osteopoikilosis. Previously reported microdeletions within this region have ranged in size from 1.83 to 10.12 Mb with a proposed 2.61 Mb smallest region of overlap containing the LEMD3, HMGA2, and GRIP1 genes. Here, we report on the identification of a 12q14 microdeletion in a female child presenting with proportionate short stature, failure to thrive, and speech delay. The genomic loss (minimum size 4.17 Mb, maximum size 4.21 Mb) contained 25 RefSeq genes including IRAK3, GRIP1, and the 3' portion of the HMGA2 gene. This is the first partial deletion of HMGA2 associated with the 12q14 microdeletion syndrome. This case further clarifies the association of LEMD3 deletions with the 12q14 microdeletion syndrome and provides additional support for the role of the HMGA2 gene in human growth.
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http://dx.doi.org/10.1002/ajmg.a.35610DOI Listing
November 2012

Microarray comparative genomic hybridization and cytogenetic characterization of tissue-specific mosaicism in three patients.

Am J Med Genet A 2012 Aug 11;158A(8):1924-33. Epub 2012 Jul 11.

Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, and The Ohio State University College of Medicine, Columbus, Ohio 43205, USA.

The presence of more than one cell line in an individual may often be missed by classical cytogenetic analysis due to a low percentage of affected cells or analysis of cells from an unaffected or less affected germ layer. Array comparative genomic hybridization (aCGH) from whole blood or tissue is an important adjunct to standard karyotyping due to its ability to detect genomic imbalances that are below the resolution of karyotype analysis. We report results from three unrelated patients in whom aCGH revealed mosaicism not identified by peripheral blood chromosome analysis. This study further illustrates the important application of aCGH in detecting tissue-specific mosaicism, thereby leading to an improvement in the ability to provide a diagnosis for patients with normal chromosome analysis and dysmorphic features, congenital anomalies, and/or developmental delay.
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http://dx.doi.org/10.1002/ajmg.a.35477DOI Listing
August 2012

Assessment of 2q23.1 microdeletion syndrome implicates MBD5 as a single causal locus of intellectual disability, epilepsy, and autism spectrum disorder.

Am J Hum Genet 2011 Oct;89(4):551-63

Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.

Persons with neurodevelopmental disorders or autism spectrum disorder (ASD) often harbor chromosomal microdeletions, yet the individual genetic contributors within these regions have not been systematically evaluated. We established a consortium of clinical diagnostic and research laboratories to accumulate a large cohort with genetic alterations of chromosomal region 2q23.1 and acquired 65 subjects with microdeletion or translocation. We sequenced translocation breakpoints; aligned microdeletions to determine the critical region; assessed effects on mRNA expression; and examined medical records, photos, and clinical evaluations. We identified a single gene, methyl-CpG-binding domain 5 (MBD5), as the only locus that defined the critical region. Partial or complete deletion of MBD5 was associated with haploinsufficiency of mRNA expression, intellectual disability, epilepsy, and autistic features. Fourteen alterations, including partial deletions of noncoding regions not typically captured or considered pathogenic by current diagnostic screening, disrupted MBD5 alone. Expression profiles and clinical characteristics were largely indistinguishable between MBD5-specific alteration and deletion of the entire 2q23.1 interval. No copy-number alterations of MBD5 were observed in 7878 controls, suggesting MBD5 alterations are highly penetrant. We surveyed MBD5 coding variations among 747 ASD subjects compared to 2043 non-ASD subjects analyzed by whole-exome sequencing and detected an association with a highly conserved methyl-CpG-binding domain missense variant, p.79Gly>Glu (c.236G>A) (p = 0.012). These results suggest that genetic alterations of MBD5 cause features of 2q23.1 microdeletion syndrome and that this epigenetic regulator significantly contributes to ASD risk, warranting further consideration in research and clinical diagnostic screening and highlighting the importance of chromatin remodeling in the etiology of these complex disorders.
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http://dx.doi.org/10.1016/j.ajhg.2011.09.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188839PMC
October 2011

Unexpected detection of dystrophin gene deletions by array comparative genomic hybridization.

Am J Med Genet A 2010 Sep;152A(9):2301-7

Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH 43205, USA.

Array comparative genomic hybridization has increasingly become the standard of care to evaluate patients for genomic imbalance. As the patient population evaluated by microarray expands, there is certain to be an increase in the detection of unexpected, yet common diseases. When array results predict a late-onset disorder or cancer predisposition, it becomes a challenge for physicians and counselors to adequately address with patients. Included in this study were three patients described with nonspecific phenotypic findings who underwent microarray testing to better define their disease etiology. An unexpected deletion within the dystrophin gene was observed in each case, despite that no patient was suspected of a dystrophinopathy at the time of testing. The patients included an 8-day-old male with a dystrophin deletion predictive of Becker muscular dystrophy, an 18-month old female found to be the carrier of deletion, and a 4-year-8-month-old male with a deletion predictive of Duchenne muscular dystrophy. In this circumstance it becomes difficult to counsel the family, as well as to predict disease course when underlying medical conditions may exist. However, early detection may enable the patient to receive proactive treatment, and allows for screening of at-risk family members. Ultimately, it is up to the clinician to promote informed decision-making within the family prior to testing, and ensure that adequate counseling is provided during follow-up.
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http://dx.doi.org/10.1002/ajmg.a.33532DOI Listing
September 2010

Identification of a recurrent microdeletion at 17q23.1q23.2 flanked by segmental duplications associated with heart defects and limb abnormalities.

Am J Hum Genet 2010 Mar 4;86(3):454-61. Epub 2010 Mar 4.

Signature Genomic Laboratories, Spokane, WA 99207, USA.

Segmental duplications, which comprise approximately 5%-10% of the human genome, are known to mediate medically relevant deletions, duplications, and inversions through nonallelic homologous recombination (NAHR) and have been suggested to be hot spots in chromosome evolution and human genomic instability. We report seven individuals with microdeletions at 17q23.1q23.2, identified by microarray-based comparative genomic hybridization (aCGH). Six of the seven deletions are approximately 2.2 Mb in size and flanked by large segmental duplications of >98% sequence identity and in the same orientation. One of the deletions is approximately 2.8 Mb in size and is flanked on the distal side by a segmental duplication, whereas the proximal breakpoint falls between segmental duplications. These characteristics suggest that NAHR mediated six out of seven of these rearrangements. These individuals have common features, including mild to moderate developmental delay (particularly speech delay), microcephaly, postnatal growth retardation, heart defects, and hand, foot, and limb abnormalities. Although all individuals had at least mild dysmorphic facial features, there was no characteristic constellation of features that would elicit clinical suspicion of a specific disorder. The identification of common clinical features suggests that microdeletions at 17q23.1q23.2 constitute a novel syndrome. Furthermore, the inclusion in the minimal deletion region of TBX2 and TBX4, transcription factors belonging to a family of genes implicated in a variety of developmental pathways including those of heart and limb, suggests that these genes may play an important role in the phenotype of this emerging syndrome.
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http://dx.doi.org/10.1016/j.ajhg.2010.01.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2833380PMC
March 2010
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