Dmitriy M Niyazov

Georgia Institute of Technology, Atlanta, Georgia, United States

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Publications (15)108.55 Total impact

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    ABSTRACT: BACKGROUND AND PURPOSE: This case series assesses the effects of five consecutive days of low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) with and without a 6-Hz primer. Although this paper studies able-bodied individuals, similar rTMS protocols are used to facilitate motor recovery in patients with hemiplegia following stroke. However, the cortical mechanisms associated with repeated daily doses of rTMS are not completely understood. CASE DESCRIPTION: Four right-handed healthy volunteers (two men, aged 20-50 years) participated in a double-blind case series of primed and unprimed rTMS. Functional magnetic resonance imaging was used to compare task-related haemodynamics during a simple motor task and resting-state cortical connectivity. Understanding the mechanisms of repeated rTMS sessions may serve as a precursor to development of rTMS paradigms involving motor cortex stimulation in patients with a range of neurologic dysfunction. OUTCOMES: Following five consecutive days of rTMS, all subjects had reduced task-related haemodynamics. Resting-state brain connectivity between motor regions was reduced only after primed rTMS. DISCUSSION: This is the first study to indicate that resting-state brain connectivity can distinguish the effect of primed and unprimed rTMS to a greater extent than task-related haemodynamics. Furthermore, priming may inhibit the connectivity between the area of the cortex underlying the rTMS site and remote brain regions. SIGNIFICANCE: These findings benefit rTMS rehabilitation studies by examining haemodynamics on repeated days of stimulation and incorporating resting-state brain connectivity analysis to further understand underlying neural mechanisms. Furthermore, this work encourages the utilization of resting connectivity in future rTMS studies. Copyright © 2011 John Wiley & Sons, Ltd.
    No preview · Article · Jun 2014 · Physiotherapy Research International
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    ABSTRACT: Ebstein anomaly is a rare congenital heart defect that most often occurs sporadically within a kindred. Familial cases, although reported, are uncommon. At this time, the genetic etiology of Ebstein anomaly is not fully elucidated. Here, we describe clinical and molecular investigations of a rare case of familial Ebstein anomaly in association with a likely pathogenic mutation of the MYH7 gene. The severity of presentation varies, and Ebstein anomaly can be observed in association with such other heart defects as ventricular septal defect and left ventricular (LV) hypertrabeculation, as seen in our family of study. In our family of study, the 31-year-old father and four of his children have been diagnosed with Ebstein anomaly. Genetic testing revealed that the father was heterozygous for the Glu1220del variant detected in exon 27 of the MYH7 gene. The MYH7 gene encodes the β-myosin heavy chain and is expressed in cardiac muscle. DNA sequencing of three of his affected children confirmed that they carried the same variant while the fourth affected child was not available for testing. This is the first report of familial Ebstein anomaly associated with the Glu1220del mutation of the MYH7 gene. The mutation segregates with disease in a family with autosomal dominant transmission of congenital heart defects including Ebstein anomaly and other associated cardiovascular defects including LV hypertrabeculation and ventricular septal defect. © 2013 Wiley Periodicals, Inc.
    No preview · Article · Dec 2013 · American Journal of Medical Genetics Part A
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    ABSTRACT: Deletions at 2p16.3 involving exons of NRXN1 are associated with susceptibility for autism and schizophrenia, and similar deletions have been identified in individuals with developmental delay and dysmorphic features. We have identified 34 probands with exonic NRXN1 deletions following referral for clinical microarray-based comparative genomic hybridization. To more firmly establish the full phenotypic spectrum associated with exonic NRXN1 deletions, we report the clinical features of 27 individuals with NRXN1 deletions, who represent 23 of these 34 families. The frequency of exonic NRXN1 deletions among our postnatally diagnosed patients (0.11%) is significantly higher than the frequency among reported controls (0.02%; P = 6.08 × 10(-7) ), supporting a role for these deletions in the development of abnormal phenotypes. Generally, most individuals with NRXN1 exonic deletions have developmental delay (particularly speech), abnormal behaviors, and mild dysmorphic features. In our cohort, autism spectrum disorders were diagnosed in 43% (10/23), and 16% (4/25) had epilepsy. The presence of NRXN1 deletions in normal parents and siblings suggests reduced penetrance and/or variable expressivity, which may be influenced by genetic, environmental, and/or stochastic factors. The pathogenicity of these deletions may also be affected by the location of the deletion within the gene. Counseling should appropriately represent this spectrum of possibilities when discussing recurrence risks or expectations for a child found to have a deletion in NRXN1. © 2013 Wiley Periodicals, Inc.
    Full-text · Article · Mar 2013 · American Journal of Medical Genetics Part A
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    ABSTRACT: Some copy-number variants are associated with genomic disorders with extreme phenotypic heterogeneity. The cause of this variation is unknown, which presents challenges in genetic diagnosis, counseling, and management. We analyzed the genomes of 2312 children known to carry a copy-number variant associated with intellectual disability and congenital abnormalities, using array comparative genomic hybridization. Among the affected children, 10.1% carried a second large copy-number variant in addition to the primary genetic lesion. We identified seven genomic disorders, each defined by a specific copy-number variant, in which the affected children were more likely to carry multiple copy-number variants than were controls. We found that syndromic disorders could be distinguished from those with extreme phenotypic heterogeneity on the basis of the total number of copy-number variants and whether the variants are inherited or de novo. Children who carried two large copy-number variants of unknown clinical significance were eight times as likely to have developmental delay as were controls (odds ratio, 8.16; 95% confidence interval, 5.33 to 13.07; P=2.11×10(-38)). Among affected children, inherited copy-number variants tended to co-occur with a second-site large copy-number variant (Spearman correlation coefficient, 0.66; P<0.001). Boys were more likely than girls to have disorders of phenotypic heterogeneity (P<0.001), and mothers were more likely than fathers to transmit second-site copy-number variants to their offspring (P=0.02). Multiple, large copy-number variants, including those of unknown pathogenic significance, compound to result in a severe clinical presentation, and secondary copy-number variants are preferentially transmitted from maternal carriers. (Funded by the Simons Foundation Autism Research Initiative and the National Institutes of Health.).
    Full-text · Article · Sep 2012 · New England Journal of Medicine
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    ABSTRACT: To understand the genetic heterogeneity underlying developmental delay, we compared copy number variants (CNVs) in 15,767 children with intellectual disability and various congenital defects (cases) to CNVs in 8,329 unaffected adult controls. We estimate that ∼14.2% of disease in these children is caused by CNVs >400 kb. We observed a greater enrichment of CNVs in individuals with craniofacial anomalies and cardiovascular defects compared to those with epilepsy or autism. We identified 59 pathogenic CNVs, including 14 new or previously weakly supported candidates, refined the critical interval for several genomic disorders, such as the 17q21.31 microdeletion syndrome, and identified 940 candidate dosage-sensitive genes. We also developed methods to opportunistically discover small, disruptive CNVs within the large and growing diagnostic array datasets. This evolving CNV morbidity map, combined with exome and genome sequencing, will be critical for deciphering the genetic basis of developmental delay, intellectual disability and autism spectrum disorders.
    Full-text · Article · Aug 2011 · Nature Genetics
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    ABSTRACT: Microdeletions of 1q43q44 result in a recognizable clinical disorder characterized by moderate to severe intellectual disability (ID) with limited or no expressive speech, characteristic facial features, hand and foot anomalies, microcephaly (MIC), abnormalities (agenesis/hypogenesis) of the corpus callosum (ACC), and seizures (SZR). Critical regions have been proposed for some of the more prominent features of this disorder such as MIC and ACC, yet conflicting data have prevented precise determination of the causative genes. In this study, the largest of pure interstitial and terminal deletions of 1q43q44 to date, we characterized 22 individuals by high-resolution oligonucleotide microarray-based comparative genomic hybridization. We propose critical regions and candidate genes for the MIC, ACC, and SZR phenotypes associated with this microdeletion syndrome. Three cases with MIC had small overlapping or intragenic deletions of AKT3, an isoform of the protein kinase B family. The deletion of only AKT3 in two cases implicates haploinsufficiency of this gene in the MIC phenotype. Likewise, based on the smallest region of overlap among the affected individuals, we suggest a critical region for ACC that contains ZNF238, a transcriptional and chromatin regulator highly expressed in the developing and adult brain. Finally, we describe a critical region for the SZR phenotype which contains three genes (FAM36A, C1ORF199, and HNRNPU). Although ~90% of cases in this study and in the literature fit these proposed models, the existence of phenotypic variability suggests other mechanisms such as variable expressivity, incomplete penetrance, position effects, or multigenic factors could account for additional complexity in some cases.
    Full-text · Article · Jul 2011 · Human Genetics
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    ABSTRACT: Reports of individuals with deletions of 1q24→q25 share common features of prenatal onset growth deficiency, microcephaly, small hands and feet, dysmorphic face and severe cognitive deficits. We report nine individuals with 1q24q25 deletions, who show distinctive features of a clinically recognizable 1q24q25 microdeletion syndrome: prenatal-onset microcephaly and proportionate growth deficiency, severe cognitive disability, small hands and feet with distinctive brachydactyly, single transverse palmar flexion creases, fifth finger clinodactyly and distinctive facial features: upper eyelid fullness, small ears, short nose with bulbous nasal tip, tented upper lip, and micrognathia. Radiographs demonstrate disharmonic osseous maturation with markedly delayed bone age. Occasional features include cleft lip and/or palate, cryptorchidism, brain and spinal cord defects, and seizures. Using oligonucleotide-based array comparative genomic hybridization, we defined the critical deletion region as 1.9 Mb at 1q24.3q25.1 (chr1: 170,135,865-172,099,327, hg18 coordinates), containing 13 genes and including CENPL, which encodes centromeric protein L, a protein essential for proper kinetochore function and mitotic progression. The growth deficiency in this syndrome is similar to what is seen in other types of primordial short stature with microcephaly, such as Majewski osteodysplastic primordial dwarfism, type II (MOPD2) and Seckel syndrome, which result from loss-of-function mutations in genes coding for centrosomal proteins. DNM3 is also in the deleted region and expressed in the brain, where it participates in the Shank-Homer complex and increases synaptic strength. Therefore, DNM3 is a candidate for the cognitive disability, and CENPL is a candidate for growth deficiency in this 1q24q25 microdeletion syndrome.
    Full-text · Article · Jun 2011 · American Journal of Medical Genetics Part A
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    Full-text · Article · Mar 2011 · Congestive Heart Failure
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    ABSTRACT: We present a case of congenital complete atrioventricular block in a preterm microcephalic male with multiple additional congenital anomalies, including spinal and rib abnormalities. The heart was structurally normal, and maternal tests for autoimmune disorders were negative. The brain had an immature lissencephalic appearance, suggestive of an insult early in gestation. Genetic testing was normal, virtually excluding chromosomal disorders that are known to cause lissencephaly. Viral studies were suggestive of cytomegalovirus infection during early gestation, and we believe that the patient's clinical presentation was most likely the result of an early cytomegalovirus infection. The finding of complete atrioventricular block in a patient with presumed cytomegalovirus infection would represent a very rare complication. "Isolated" complete atrioventricular block in a fetus should be considered an incentive for an extensive work-up in search for a possible etiology, rather than accepted as a final diagnosis.
    No preview · Article · Sep 2010 · Congenital Heart Disease
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    ABSTRACT: It is important to recognize the possibility of a syndromic etiology of cardiac defects when dysmorphic features and other congenital defects are present. We report a patient who presented with atrial fibrillation and was found to have an abnormal mitral valve, congenital aneurysm of the left atrial appendage, and features consistent with both Cardiofaciocutaneous syndrome and Noonan syndrome. The congenital aneurysm of the left atrial appendage was a previously unreported cardiac presentation for either syndrome. Diagnostic considerations based upon his genotype and phenotype are discussed, along with his unique cardiac presentation and treatment.
    No preview · Article · Jan 2010 · Congenital Heart Disease
  • Laura L Hayes · Stephen F Simoneaux · Susan Palasis · Dmitriy M Niyazov
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    ABSTRACT: The oral-facial-digital syndromes (OFDS) comprise a group of disorders involving malformations of the mouth, face, and digits. There are 13 subtypes of the OFDS, and much overlap exists among OFDS patients. Distinct syndromes such as Joubert and Pallister-Hall display many of the same features. This report describes an infant with abnormalities including a hypoplastic/absent cerebellar vermis and forked third metacarpals, consistent with a diagnosis of OFDS type VI (Váradi-Papp). The girl's abnormalities also included malformations of the larynx and trachea, findings never before described in type VI but described in other OFDS subtypes and similar syndromes. Our patient represents a transitional OFDS type, further supporting evidence of a common molecular pathway among these disorders. This report highlights the importance of the radiologist's role in diagnosis.
    No preview · Article · Jun 2008 · Pediatric Radiology
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    ABSTRACT: Subtelomeric imbalances have been implicated in developmental delay and mental retardation (MR) and described for most chromosomes. This study reports the first detailed description of two individuals with de novo 12q subtelomere deletions and high-resolution mapping of their deletion size with oligonucleotide array CGH for genotype/phenotype comparisons. Patient 1 is an 8-year-old male with borderline mild MR, food-seeking behavior, obesity, no significant dysmorphic facial features, abnormal hair whorl pattern, brachydactyly and mild clinodactyly. Patient 2 is a 12-year-old male with mild MR, food-seeking behavior, obesity, short stature, mild dysmorphic facial features, multicystic kidney and unilateral cryptorchidism. Both patients share a deleted region of approximately 1.6 Mb, including 14 known genes, which perhaps contributed to their similar phenotypes. However, Patient 2 has more severe MR and organ system involvement, possibly due to the larger deletion size ( approximately 4.5 Mb) including an additional eight genes, although it is difficult to make phenotype/genotype correlations based on only two patients. Due to the relatively mild presentation of both of our patients, we propose that a proportion of individuals with subtelomeric imbalances may go undetected and therefore, recommend subtelomeric studies be carried out for cases of unexplained mild MR or isolated learning disability (LD) with behavioral problems in the absence of major dysmorphic features or birth defects. In addition, 12q subtelomeric deletions should be considered in the differential diagnosis of patients presenting with food-seeking behavior and resultant obesity, as well as those referred to rule out Prader-Willi syndrome.
    Full-text · Article · Nov 2007 · American Journal of Medical Genetics Part A
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    ABSTRACT: Muscle fatigue has been known to differentially affect the activation level of the primary motor cortices (MIs) of the brain's two hemispheres. Whether this fatigue-related decoupling influence on the motor cortical signals extends beyond the motor action to the after-fatigue-task resting state is unknown. This question can be addressed by analyzing functional connectivity (FC) of low-frequency oscillations of resting-state functional MRI (fMRI) signals of the MIs. Low-frequency oscillations (<0.08 Hz) have been detected in many fMRI studies and appear to be synchronized between functionally related areas. These patterns of FC have been shown to differ between normal and various pathological states. The purpose of this study was to examine muscle fatigue-induced resting-state interhemispheric motor cortex FC changes in healthy subjects. We hypothesized that muscle fatigue would create a temporary "disrupted state" in the brain, and would decrease resting state interhemispheric motor cortical FC. Ten healthy subjects performed repetitive unilateral handgrip contractions that induced significant muscle fatigue, with resting state fMRI data collected before and after the task. After excluding two subjects due to gross head motion, interhemispheric motor cortex FC was assessed by cross-correlating the MI fMRI signal time courses. We found that the number of significant interhemispheric correlations in the MI fMRI signals decreased significantly after the performance of the fatigue task. These results suggest that resting state interhemispheric motor cortex FC may be used as an index of recovery from fatigue.
    No preview · Article · Oct 2005 · Brain Research
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    D.M. Niyazov · A.J. Butler · Y.M. Kadah · C.M. Epstein · X.P. Hu
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    ABSTRACT: To compare fMRI activations during movement and motor imagery to corresponding motor evoked potential (MEP) maps obtained with the TMS coil in three different orientations. fMRI activations during executed (EM) and imagined (IM) movements of the index finger were compared to MEP maps of the first dorsal interosseus (FDI) muscle obtained with the TMS coil in anterior, posterior and lateral handle positions. To ensure spatial registration of fMRI and MEP maps, a special grid was used in both experiments. No statistically significant difference was found between the TMS centers of gravity (TMS CoG) obtained with the three coil orientations. There was a significant difference between fMRI centers of gravity during IMs (IM CoG) and EMs (EM CoG), with IM CoGs localized on average 10.3mm anterior to those of EMs in the precentral gyrus. Most importantly, the IM CoGs closely matched cortical projections of the TMS CoGs while the EM CoGs were on average 9.5mm posterior to the projected TMS CoGs. TMS motor maps are more congruent with fMRI activations during motor imagery than those during EMs. These findings are not significantly affected by changing orientation of the TMS coil. Our results suggest that the discrepancy between fMRI and TMS motor maps may be largely due to involvement of the somatosensory component in the EM task.
    Full-text · Article · Aug 2005 · Clinical Neurophysiology
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    ABSTRACT: Synchronized oscillations in resting state timecourses have been detected in recent fMRI studies. These oscillations are low frequency in nature (< 0.08 Hz), and seem to be a property of symmetric cortices. These fluctuations are important as a potential signal of interest, which could indicate connectivity between functionally related areas of the brain. It has also been shown that the synchronized oscillations decrease in some spontaneous pathological states. Thus, detection of these functional connectivity patterns may help to serve as a gauge of normal brain activity. The cognitive effects of muscle fatigue are not well characterized. Sustained fatigue has the potential to dynamically alter activity in brain networks. In this work, we examined the interhemispheric correlations in the left and right primary motor cortices and how they change with muscle fatigue. Resting-state functional MRI imaging was done before and after a repetitive unilateral fatigue task. We find that the number of significant correlations in the bilateral motor network decreases with fatigue. These results suggest that resting-state interhemispheric motor cortex functional connectivity is affected by muscle fatigue.
    No preview · Article · Apr 2005 · Proceedings of SPIE - The International Society for Optical Engineering

Publication Stats

824 Citations
108.55 Total Impact Points

Institutions

  • 2014
    • Georgia Institute of Technology
      • Department of Biomedical Engineering
      Atlanta, Georgia, United States
  • 2013
    • Louisiana State University Health Sciences Center New Orleans
      New Orleans, Louisiana, United States
  • 2011-2013
    • Ochsner
      • Department of Pediatrics
      New Orleans, Louisiana, United States
  • 2005-2008
    • Emory University
      • • Department of Human Genetics
      • • Department of Biomedical Engineering
      Atlanta, Georgia, United States