Marjan M. Nezarati
A5037801888- Genomic variations and chromosomal abnormalities
- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Glycogen Storage Diseases and Myoclonus
- Biochemical and Molecular Research
- Congenital heart defects research
- Epigenetics and DNA Methylation
- Genetic Syndromes and Imprinting
- RNA modifications and cancer
- Metabolism and Genetic Disorders
- Alkaline Phosphatase Research Studies
- Cholesterol and Lipid Metabolism
- Cancer-related gene regulation
- Cleft Lip and Palate Research
- Genetic and Kidney Cyst Diseases
- DNA Repair Mechanisms
- Amino Acid Enzymes and Metabolism
- Connective tissue disorders research
- Prenatal Screening and Diagnostics
- Hedgehog Signaling Pathway Studies
- Lysosomal Storage Disorders Research
- Peroxisome Proliferator-Activated Receptors
- Congenital Diaphragmatic Hernia Studies
- Folate and B Vitamins Research
- Hereditary Neurological Disorders
North York General Hospital
2014-2024
University of Toronto
2005-2024
York General Hospital
2009-2024
Mount Sinai Hospital
2015-2016
Harvard University
2012
Howard Hughes Medical Institute
2012
Hospital for Sick Children
2001-2011
SickKids Foundation
2002-2006
Auckland City Hospital
2006
Alberta Children's Hospital
1999
Some copy-number variants are associated with genomic disorders extreme phenotypic heterogeneity. The cause of this variation is unknown, which presents challenges in genetic diagnosis, counseling, and management.We analyzed the genomes 2312 children known to carry a variant intellectual disability congenital abnormalities, using array comparative hybridization.Among affected children, 10.1% carried second large addition primary lesion. We identified seven disorders, each defined by specific...
Abstract The clinical phenotype of Ligase IV syndrome (LIG4 syndrome), an extremely rare autosomal recessive condition caused by mutations in the LIG4 gene, closely resembles that Nijmegen breakage (NBS), and is characterized microcephaly, characteristic facial features, growth retardation, developmental delay, immunodeficiency. We report a 4½‐year‐old boy who presented with acute T‐cell leukemia. gestalt was strongly reminiscent NBS. patient died shortly after onset treatment for his...
<h3>Background</h3> Mutations in the <i>KIAA2022</i> gene have been reported male patients with X-linked intellectual disability, and related female carriers were unaffected. Here, we report 14 who carry a heterozygous de novo mutation share phenotype characterised by disability epilepsy. <h3>Methods</h3> Reported females selected for genetic testing because of substantial developmental problems and/or X-inactivation expression studies performed when possible. <h3>Results</h3> All mutations...
Despite large sequencing and data sharing efforts, previously characterized pathogenic variants only account for a fraction of Mendelian disease patients, which highlights the need accurate identification interpretation novel variants. In cohort 4577 molecularly families, numerous scenarios in variant can be challenging are encountered. We describe categories challenges that cover phenotype (e.g. allelic disorders), pedigree structure imprinting disorders masquerading as autosomal recessive...
Abstract Persistent hyperphosphatasia associated with developmental delay and seizures was described in a single family by Mabry et al. 1970 (OMIM 239300), but the nosology of this condition has remained uncertain ever since. We report on five new patients (two siblings, one offspring consanguineous parents, two sporadic patients) that help delineate distinctive disorder provide evidence favor autosomal recessive inheritance. Common to all is facial dysmorphism, namely hypertelorism, broad...
Abstract Hyperphosphatasia with neurologic deficit (Mabry syndrome) was first described in a single family (OMIM#239300) by Mabry et al. [ 1970 ]. Although considered rare at the time, more than 20 individuals triad of developmental disability, seizures, and hyperphosphatasia have been identified world‐wide. The 1‐6 mannosyltransferase 2, phosphatidylinositol glycan V ( PIGV ) gene has found to be disrupted some patients additional feature brachytelephalangy. In present report we identify...
Visceral myopathy with abnormal intestinal and bladder peristalsis includes a clinical spectrum megacystis-microcolon hypoperistalsis syndrome chronic pseudo-obstruction. The vast majority of cases are caused by dominant variants in ACTG2; however, the overall genetic architecture visceral has not been well-characterized. We ascertained 53 families, based on megacystis, functional bladder/gastrointestinal obstruction, or microcolon. A combination targeted ACTG2 sequencing exome was used....
Au-Kline syndrome (AKS) is a neurodevelopmental disorder associated with multiple malformations and characteristic facial gestalt. The first individuals ascertained carried de novo loss-of-function (LoF) variants in HNRNPK. Here, we report 32 AKS (26 previously unpublished), including 13 missense variants. We propose new clinical diagnostic criteria for that differentiate it from the clinically overlapping Kabuki describe significant phenotypic expansion to include who present subtle...
Abstract Chung-Jansen syndrome is a neurodevelopmental disorder characterized by intellectual disability, behavioral problems, obesity and dysmorphic features. It caused pathogenic variants in the PHIP gene that encodes for Pleckstrin homology domain-interacting protein, which part of an epigenetic modifier protein complex. Therefore, we hypothesized haploinsufficiency may impact genome-wide DNA methylation (DNAm). We assessed DNAm profiles affected individuals with likely Infinium...
Abstract The etiology of mental retardation (MR), often presenting as developmental delay in childhood, is unknown approximately one‐half cases. G‐banding the standard method for investigating those suspected having a chromosomal etiology; however, detection structural abnormalities limited by size and pattern G‐bands involved. Rearrangements involving subtelomeric regions have been shown to cause MR this has generated interest prevalence these rearrangements using telomere‐specific probes....
Nicotinamide adenine dinucleotide (NAD) is an essential coenzyme involved in over 400 cellular reactions. During embryogenesis, mammals synthesize NAD de novo from dietary l -tryptophan via the kynurenine pathway. Biallelic, inactivating variants three genes encoding enzymes of this biosynthesis pathway (KYNU, HAAO, and NADSYN1) disrupt synthesis have been identified patients with multiple malformations heart, kidney, vertebrae, limbs; these Congenital Deficiency Disorder HAAO four families...
To identify copy number variant (CNV) causes of periventricular nodular heterotopia (PNH) in patients for whom FLNA sequencing is negative.Screening 35 from 33 pedigrees on an Affymetrix 6.0 microarray led to the identification one individual bearing a CNV that disrupted FLNA. FLNA-disrupting CNVs were also isolated 2 other individuals by multiplex ligation probe amplification. These 3 cases further characterized high-resolution oligo array comparative genomic hybridization (CGH), and...
Human dysmorphology syndromes are frequently defined by characteristic abnormalities in facial morphogenesis. Two such well recognized the oculoauriculovertebral spectrum (OAVS) and frontonasal dysplasia (FND). OAVS is diagnosed on basis of presence typical features which can include microtia, preauricular tags, hemifacial microsomia, lateral face clefting, epibulbar dermoids, upper palpebral colobomata. FND characterized ocular hypertelorism, nasal anterior cranium bifidum occultum. After...
Most cases of the VACTERL “association” [Martínez-Frías et al., Am. J. Med. Genet. 76:291–296, 1998] are sporadic, with an empiric recurrence risk 1% or less. Rare families VACTERL-H association described patterns consistent single gene inheritance. Also occasional anomalies in sibs parents affected individuals. We describe a mother and son typical anomalies. The patient was born by cesarean section to 27-year-old G1 following uncomplicated pregnancy. He found have asymmetric crying face,...
ABSTRACT Objectives The objective of this study is to describe the prenatal sonographic features and results DNA analysis on three fetuses with dyssegmental dysplasia, Silverman‐Handmaker type (DD‐SH). Methods A retrospective review confirmed DD‐SH was conducted. fetal ultrasound findings, radiological characteristics, mutation heparan sulphate perlecan gene 2 ( HSPG2 ) were reviewed. Results There cases in two families diagnosed prenatally. main severe limb shortening vertebral segmentation...
Abstract The Smith‐Lemli‐Opitz syndrome (SLOS), or RSH syndrome, is a well‐characterized multiple congenital anomalies/mental retardation syndrome. phenotype has been redefined to include mildly affected individuals with minor anomalies and developmental delay, severe malformations pre‐ perinatal mortality. condition due the deficient activity of enzyme 7‐dehydrocholesterol (7‐DHC) reductase [Shefer et al., 1995 : J Clin Invest 96:1779–1785], gene mapped chromosome 11q13 [Moebius 1998 Proc...