Paul R. Mark
A5080429540- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- Epigenetics and DNA Methylation
- Ion channel regulation and function
- Ion Transport and Channel Regulation
- Congenital Diaphragmatic Hernia Studies
- Prenatal Screening and Diagnostics
- Cancer-related gene regulation
- RNA modifications and cancer
- RNA Research and Splicing
- Cellular transport and secretion
- Congenital heart defects research
- Connective tissue disorders research
- Erythrocyte Function and Pathophysiology
- Congenital limb and hand anomalies
- Pancreatic function and diabetes
- Receptor Mechanisms and Signaling
- Congenital Heart Disease Studies
- Chromatin Remodeling and Cancer
- Microtubule and mitosis dynamics
- Nursing Roles and Practices
- Hereditary Neurological Disorders
- Tissue Engineering and Regenerative Medicine
- Fetal and Pediatric Neurological Disorders
Northwell Health
2024-2025
Corewell Health
2023-2025
Helen DeVos Children's Hospital
2021-2024
Corewell Health Blodgett Hospital
2016-2022
Michigan State University
2021-2022
Spectrum Health
2013-2022
Denver School of Nursing
2022
Triangle
2022
Indianapolis Zoo
2022
Gainesville Obstetrics & Gynecology
2022
Congenital malformations can be manifested as combinations of phenotypes that co-occur more often than expected by chance. In many such cases, it has proved difficult to identify a genetic cause. We sought the cause cardiac, vertebral, and renal defects, among others, in unrelated patients.We used genomic sequencing potentially pathogenic gene variants families which person had multiple congenital malformations. tested function variant using assays vitro enzyme activity quantifying...
ADNP syndrome is a rare Mendelian disorder characterized by global developmental delay, intellectual disability, and autism. It caused truncating mutations in ADNP, which involved chromatin regulation. We hypothesized that the disruption of regulation might result specific DNA methylation patterns could be used molecular diagnosis syndrome. identified two distinct partially opposing genomic episignatures peripheral blood samples from 22 patients with The "epi-ADNP-1" episignature included ~...
Smooth muscle dysfunction syndrome (SMDS) due to heterozygous ACTA2 arginine 179 alterations is characterized by patent ductus arteriosus, vasculopathy (aneurysm and occlusive lesions), pulmonary arterial hypertension, other complications in smooth muscle-dependent organs. We sought define the clinical history of SMDS develop recommendations for evaluation management.Medical records 33 patients with (median age 12 years) were abstracted analyzed.All had congenital mydriasis related pupillary...
Germline loss-of-function variants in CTNNB1 cause neurodevelopmental disorder with spastic diplegia and visual defects (NEDSDV; OMIM 615075) are the most frequent, recurrent monogenic of cerebral palsy (CP). We investigated range clinical phenotypes owing to disruptions determine association between NEDSDV CP.Genetic information from 404 individuals collectively 392 pathogenic were ascertained for study. From these, detailed 52 previously unpublished collected combined 68 published...
Ciliopathies are an extensive group of autosomal recessive or X-linked disorders with considerable genetic and clinical overlap, which collectively share multiple organ involvement may result in lethal viable phenotypes. In large numbers cases the defect remains yet to be determined. The aim this study is describe mutational frequency phenotypic spectrum CEP120 gene.
To investigate the effect of PLXNA1 variants on phenotype patients with autosomal dominant and recessive inheritance patterns to functionally characterize zebrafish homologs plxna1a plxna1b during development.We assembled ten from seven families biallelic or de novo variants. We describe genotype-phenotype correlations, investigated by structural modeling, used Morpholino knockdown experiments in embryonic role plxna1b.Shared phenotypic features among include global developmental delay...
Abstract Congenital NAD deficiency disorder (CNDD) is a multisystem condition in which cardiac, renal, vertebral, and limb anomalies are most common, but all organ systems have been identified. Patients with this biallelic pathogenic variants involving genes the nicotinamide adenine dinucleotide (NAD + ) synthesis pathway leading to decreased systemic levels. CNDD mimic clinical features described vertebral-anal-cardiac-tracheoesophageal fistula-renal-limb (VACTERL) association raising...
Abstract Sleep apnea is a common disorder that represents global public health burden. KCNK3 encodes TASK-1, K + channel implicated in the control of breathing, but its link with sleep remains poorly understood. Here we describe new developmental associated (developmental delay apnea, or DDSA) caused by rare de novo gain-of-function mutations . The cluster around ‘X-gate’, gating motif controls opening, and produce overactive channels no longer respond to inhibition G-protein-coupled...
The wobble position in the anticodon loop of transfer ribonucleic acid (tRNA) is subject to numerous posttranscriptional modifications. In particular, thiolation uridine has been shown play an important role codon-anticodon interactions. This modification catalyzed by a highly conserved CTU1/CTU2 complex, disruption which cause abnormal phenotypes yeast, worms, and plants. We have previously suggested that single founder splicing variant human CTU2 causes novel multiple congenital anomalies...
Abstract Genetic variants in chromatin regulators are frequently found neurodevelopmental disorders, but their effect disease etiology is rarely determined. Here, we uncover and functionally define pathogenic the modifier EZH1 as cause of dominant recessive disorders 19 individuals. encodes one two alternative histone H3 lysine 27 methyltransferases PRC2 complex. Unlike other subunits, which involved cancers developmental syndromes, implication human development largely unknown. Using...
We recently described a new neurodevelopmental syndrome (TAF1/MRXS33 intellectual disability [ID] syndrome) (MIM# 300966) caused by pathogenic variants involving the X-linked gene TATA-box binding protein associated factor 1 (TAF1), which participates in RNA polymerase II transcription. The initial study reported 11 families, and was defined as presenting early life with hypotonia, facial dysmorphia, developmental delay that evolved into ID and/or autism spectrum disorder. have now...
Pleiotropy is defined as the phenomenon of a single gene locus influencing two or more distinct phenotypic traits. However, nicotinamide adenine dinucleotide (NAD+) deficiency through diet alone can cause multiple malformations in mice. Additionally, humans with decreased NAD+ production due to changes pathway genes display similar malformations. Here, I hypothesize pleiotropic mechanism for malformation conditions, including limb-body wall complex (LBWC), pentalogy Cantrell (POC),...
Highly conserved TREX-mediated mRNA export is emerging as a key pathway in neuronal development and differentiation. TREX subunit variants cause neurodevelopmental disorders (NDDs) by interfering with from the cell nucleus to cytoplasm. Previously we implicated four missense X-linked THOC2 gene intellectual disability (ID). We now report an additional six affected individuals five unrelated families two de novo three maternally inherited pathogenic or likely extending genotypic phenotypic...
Abstract While inherited hemizygous variants in PHF6 cause X‐linked recessive Borjeson‐Forssman‐Lehmann syndrome (BFLS) males, de novo heterozygous females are associated with an overlapping but distinct phenotype, including moderate to severe intellectual disability, characteristic facial dysmorphism, dental, finger and toe anomalies, linear skin pigmentation. By personal communication colleagues, we assembled 11 additional BFLS due . We confirm the phenotype include variable recognizable...
Abstract Heterozygous sequence variants of the COL2A1 gene cause a phenotypic spectrum collectively called type II collagenopathies. Here, we describe variant, c.2957C>T, p.Pro986Leu in triple helical domain, which is Y‐position substitution exon 41 repeating triplet Gly‐X‐Y proα1(II) chain. This variant was associated with mild spondyloepiphyseal dysplasia phenotype three individuals three‐generation family. On clinical examination at age 19 months, proband had flat face, bifid uvula,...
Abstract Histone Gene Cluster 1 Member E, HIST1H1E , encodes H1.4, is one of a family epigenetic regulator genes, acts as linker histone protein, and responsible for higher order chromatin structure. syndrome (also known Rahman syndrome, OMIM #617537) recently described intellectual disability (ID) syndrome. Since the initial description five unrelated individuals with three different heterozygous protein‐truncating variants (PTVs) in gene 2017, we have recruited 30 patients, all PTVs that...