scholarly journals Partial Trisomy 13q/Monosomy 3p Resulting from a Paternal Reciprocal 3p;13q Translocation in a Boy with Facial Dysmorphism and Hypertrophic Cardiomyopathy

2021 ◽  
pp. 1-7
Author(s):  
Monica Martin-de Saro ◽  
Zyndia Compean ◽  
Karina Aguilar ◽  
Luz María González-Huerta ◽  
Lautaro Plaza-Benhumea ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Hypertrophic Cardiomyopathy ◽  
Phenotypic Expression ◽  
Clinical Manifestations ◽  
Partial Trisomy ◽  
Trisomy 13 ◽  
Cardiac Insufficiency ◽  
Facial Dysmorphism ◽  
Chromosomal Imbalance ◽  
Microarray Assay

Individuals with 3p deletion show a great clinical variability. Apparently, a 1.5-Mb terminal deletion, including the <i>CRBN</i> and <i>CNTN4</i> genes, is sufficient to cause this syndrome. Partial trisomy 13q is a rare chromosomal abnormality with a variable phenotypic expression, but in most cases, patients have a phenotype resembling complete trisomy 13. The aim of the present study is to describe a 9-month-old Mexican male patient with 3p deletion/13q duplication and a novel clinical finding. He presented with facial dysmorphism and multiple congenital alterations. Echocardiogram revealed cardiac insufficiency with hypertrophic cardiomyopathy and pulmonary hypertension, not previously reported. Karyotype from the patient and his father were 46,XY,add(3)(p26) and 46,XY,t(3;13), respectively. Microarray assay of the proband exhibited an approximately 2.6-Mb loss at terminal 3p26.3 and a 27.7-Mb gain of the long arm in terminal chromosome 13 at q31.1q34. A chromosomal imbalance with a partial trisomy 13q31.1q34 and monosomy 3p26.3 of paternal origin were detected. Microarray assay of both parents were normal. The proband has a cardiomyopathy not previously reported. These data enrich the spectrum of clinical manifestations in 3p deletion/3q duplication chromosomopathy.

scholarly journals Partial Trisomy of Chromosome 13 with a Novel Translocation (8 ; 13) and Unique Clinical Presentation in a Palestinian Infant

2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Allam Abuhamda ◽  
Aymen Elsous ◽  
Fadel A. Sharif
Keyword(s):  
Cytogenetic Study ◽  
Left Lung ◽  
Clinical Manifestations ◽  
Lower Lobe ◽  
Partial Trisomy ◽  
Chromosome 8 ◽  
Trisomy 13 ◽  
Normal Vaginal Delivery ◽  
Global Developmental Delay ◽  
Partial Monosomy

Partial trisomy 13 is a rare syndrome that usually culminates in death within the first six months of the infant’s life. We present a rare case of partial trisomy 13q with exclusive clinical manifestations. The full-term male baby was born by normal vaginal delivery, his birth weight was 3500 grams, and head circumference was 30 cm. He had dysmorphic features in the form of microcephaly, trigonocephaly, depressed nose bridge, hypotelorism, long philtrum, high arch palate, left-sided inguinal hernia, hydrocele, and laryngomalacia. He was operated for pyloric stenosis at the age of 28 days. He also had left-sided severe pelvic-ureteral junction stenosis which was repaired by nephrostomy followed by pyeloplasty. Furthermore, he had right-sided vesicoureteral reflux grade III, right-sided hydronephrosis, small ventricular septum defect, small atrial septum defect, left lung lower lobe sequestration, and craniosynostosis of metopic suture. The baby had global developmental delay and failure to thrive. Cytogenetic study showed a 46,XY, der(8)t(8;13)(p23;q14) karyotype, emphasizing a partial trisomy 13q syndrome with a concomitant partial monosomy in 8p. The baby passed away, in the intensive care unit, at the age of 7 months due to respiratory failure resulting from recurrent chest infections. This is the first reported case of a partial trisomy 13q associated with chromosome 8 with unique clinical presentations. Cytogenetic study for both parents is recommended in order to pinpoint the origin of the translocation and to provide the proper counseling for the family.

Knobloch Syndrome in Siblings with Posterior Fossa Malformations Along with Cerebellar Midline Cleft Abnormality Caused by Biallelic COL18A1 Mutation: Case-Based Review

2020 ◽  
Author(s):  
Siddaramappa J. Patil ◽  
Shruti Pande ◽  
Jyoti Matalia ◽  
Venkatraman Bhat ◽  
Minal Kekatpure ◽  
...  
Keyword(s):  
Posterior Fossa ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Later Life ◽  
Facial Dysmorphism ◽  
Ocular Manifestations ◽  
Occipital Encephalocele ◽  
Knobloch Syndrome ◽  
Posterior Fossa Malformations ◽  
Midline Cleft

AbstractKnobloch syndrome (KS) is an autosomal recessive disorder caused by biallelic pathogenic variants in COL18A1. KS clinically manifests with the typical eye findings (high myopia, vitreoretinal degeneration, retinal detachment, and lens subluxation), variable neurological findings (occipital encephalocele, polymicrogyria, cerebellar malformations, epilepsy, and intellectual disability), and the other uncommon clinical manifestations. Literature review of all KS patients (source PubMed) was done with special reference to cerebellar abnormalities. Here, we report two siblings with typical KS with posterior fossa malformations and novel cerebellar midline cleft abnormality analyzed by whole exome sequencing. Known pathogenic homozygous variant c.2908C > T; (p.Arg970Ter) in exon 26 of COL18A1 was found as a cause for KS. These two siblings presented with early-onset severe ocular manifestations, facial dysmorphism, and variable central nervous system manifestations along with novel cerebellar midline cleft abnormality. The presence or absence of structural brain malformations and genotypes does not absolutely predict cognitive functions in KS patients. However, the presence of posterior fossa abnormality may be predictive for the development of ataxia in later life and needs further studies.

scholarly journals The Role of JAK/STAT Molecular Pathway in Vascular Remodeling Associated with Pulmonary Hypertension

2021 ◽  
Vol 22 (9) ◽  
pp. 4980
Author(s):  
Inés Roger ◽  
Javier Milara ◽  
Paula Montero ◽  
Julio Cortijo
Keyword(s):  
Pulmonary Hypertension ◽  
Smooth Muscle ◽  
Pulmonary Artery ◽  
Vascular Remodeling ◽  
Pulmonary Arteries ◽  
Clinical Manifestations ◽  
Different Types ◽  
Artery Remodeling ◽  
Stat Pathway ◽  
Pulmonary Artery Remodeling

Pulmonary hypertension is defined as a group of diseases characterized by a progressive increase in pulmonary vascular resistance (PVR), which leads to right ventricular failure and premature death. There are multiple clinical manifestations that can be grouped into five different types. Pulmonary artery remodeling is a common feature in pulmonary hypertension (PH) characterized by endothelial dysfunction and smooth muscle pulmonary artery cell proliferation. The current treatments for PH are limited to vasodilatory agents that do not stop the progression of the disease. Therefore, there is a need for new agents that inhibit pulmonary artery remodeling targeting the main genetic, molecular, and cellular processes involved in PH. Chronic inflammation contributes to pulmonary artery remodeling and PH, among other vascular disorders, and many inflammatory mediators signal through the JAK/STAT pathway. Recent evidence indicates that the JAK/STAT pathway is overactivated in the pulmonary arteries of patients with PH of different types. In addition, different profibrotic cytokines such as IL-6, IL-13, and IL-11 and growth factors such as PDGF, VEGF, and TGFβ1 are activators of the JAK/STAT pathway and inducers of pulmonary remodeling, thus participating in the development of PH. The understanding of the participation and modulation of the JAK/STAT pathway in PH could be an attractive strategy for developing future treatments. There have been no studies to date focused on the JAK/STAT pathway and PH. In this review, we focus on the analysis of the expression and distribution of different JAK/STAT isoforms in the pulmonary arteries of patients with different types of PH. Furthermore, molecular canonical and noncanonical JAK/STAT pathway transactivation will be discussed in the context of vascular remodeling and PH. The consequences of JAK/STAT activation for endothelial cells and pulmonary artery smooth muscle cells’ proliferation, migration, senescence, and transformation into mesenchymal/myofibroblast cells will be described and discussed, together with different promising drugs targeting the JAK/STAT pathway in vitro and in vivo.

The link between hidradenitis suppurativa and phylloid hypomelanosis in partial trisomy‐13 mosaicism: New evidences and further genetic/pathogenetic insights

2021 ◽  
Author(s):  
Riccardo Forconi ◽  
Stefania Bigoni ◽  
Lucrezia Pacetti ◽  
Cristina Host ◽  
Natale Schettini ◽  
...  
Keyword(s):  
Hidradenitis Suppurativa ◽  
Partial Trisomy ◽  
Trisomy 13

scholarly journals 170 Ethnic differences in phenotypic expression of hypertrophic cardiomyopathy

Heart ◽  
2011 ◽  
Vol 97 (Suppl 1) ◽  
pp. A95-A95 ◽  
Author(s):  
N. Sheikh ◽  
M. Papadakis ◽  
N. Chandra ◽  
H. Raju ◽  
A. Zaidi ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Ethnic Differences ◽  
Phenotypic Expression

scholarly journals A novel TNNI3 gene mutation (c.235C>T/ p.Arg79Cys) found in a thirty-eight-year-old women with hypertrophic cardiomyopathy

2018 ◽  
Vol 13 (1) ◽  
pp. 374-378 ◽  
Author(s):  
Qin Tao ◽  
Junhua Yang ◽  
Weili Cheng ◽  
Shenghua Yu ◽  
Xu Fang ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Gene Mutation ◽  
Troponin I ◽  
Clinical Manifestations ◽  
Genetic Mutation ◽  
Heterozygous Mutation ◽  
Her Family ◽  
Slow Development ◽  
Magnetic Resonance Imaging Mri ◽  
Dimensional Echocardiography

AbstractWe report the case of a thirty-eight-year-old woman admitted to our hospital due to palpitation and chest distress. ST-T segment change was found in her ECG. She was then diagnosed with hypertrophic cardiomyopathy by two-dimensional echocardiography. Physical examination showed no obvious abnormal signs and all laboratory examinations were within the normal range. Myocardial fibrosis was detected by cardiac magnetic resonance imaging (MRI). A novel heterozygous mutation (c.235C>T/p.Arg79Cys) in TNNI3 for cardiac troponin I was identified in her. Subsequently, her families were investigated. No one died suddenly in her family. Her father, one of her siblings and one of her daughters had the same genetic mutation but with different clinical manifestations while the others were healthy. Her father and brother were also diagnosed with hypertrophic cardiomyopathy with different clinical manifestation. However, the echocardiography of her daughter was absolutely normal. We hypothesized that the Arg79Cys mutation in TNNI3 leads to a slow development of cardiac hypertrophy and the phenotype of this gene mutation is diverse.

scholarly journals Marginal zone B-cell lymphomas of different sites share similar cytogenetic and morphologic features [see comments]

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 299-307 ◽  
Author(s):  
J Dierlamm ◽  
S Pittaluga ◽  
I Wlodarska ◽  
M Stul ◽  
J Thomas ◽  
...  
Keyword(s):  
B Cell ◽  
Structural Changes ◽  
Marginal Zone ◽  
Chromosomal Abnormalities ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
B Cell Lymphoma ◽  
Partial Trisomy ◽  
Chromosome 1 ◽  
Chromosomal Changes

Clinical, histologic, cytogenetic, and molecular genetic data of 31 patients with extranodal, nodal, and splenic marginal zone B-cell lymphoma (MZBCL) are presented. Despite these variable clinical manifestations, a similar spectrum of morphologic features as well as distinctive immunophenotypic findings were noted. In all cases, a monotypic B-cell proliferation consistently negative for CD5, CD10, and CD23 was found expanding the marginal zone of the B follicle with and without colonization of the follicle centers. Clonal chromosomal abnormalities were detected in 23 of the 31 patients. Recurrent aberrations included whole or partial trisomy 3 (18 cases), trisomy 18 (9 cases), and structural rearrangements of chromosome 1 with breakpoints in 1q21 (9 cases) or 1p34 (6 cases), all of which were seen in extranodal, nodal, as well as splenic MZBCL. Abnormalities of the additional chromosome 3, such as +del(3)(p13),+i(3)(q10), or structural changes involving the distal part of the long arm, were evident in 9 of the 18 cases. All recurrent abnormalities were found in MZBCL more frequently than in other histologic entities of B-cell non-Hodgkin's lymphoma (B-NHL). None of the known lymphoma-associated chromosomal changes or rearrangements of the BCL1, BCL2, BCL3, BCL6, and CMYC genes were detected. We conclude that MZBCL represent a distinct entity of B- NHL with characteristic morphologic and immunophenotypic features and particular chromosomal abnormalities, and that a close histogenetic relationship between extranodal, nodal, and splenic MZBCL is likely, although the clinical presentation may vary.

scholarly journals Atrial Fibrillation in Hypertrophic Cardiomyopathy

2021 ◽  
Vol 11 (3) ◽  
pp. 173-185
Author(s):  
G. A. Ignatenko ◽  
G. G. Taradin ◽  
N. T. Vatutin ◽  
A. A. Kaluga ◽  
Yu. D. Kostyamin
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Radiofrequency Ablation ◽  
Hypertrophic Cardiomyopathy ◽  
Sinus Rhythm ◽  
Antiarrhythmic Drugs ◽  
Contemporary Literature ◽  
Clinical Manifestations ◽  
Detection Methods

The current information about features of atrial fibrillation in patients with hypertrophic cardiomyopathy is presented in this review. The data about prevalence, pathogenesis and its various complications in these patients are disclosed. The article contains updated clinical recommendations of authoritative medical societies on the discussing problem. There is detailed discussion of risk factors of atrial fibrillation onset in setting of hypertrophic cardiomyopathy with demonstration of results of different studies concerning to investigation of relationship between risk factors and probability of the arrhythmia development. There is description of detection methods, clinical manifestations, and the course of atrial fibrillation in patients with hypertrophic cardiomyopathy. The contemporary literature data are presented regarding to the management of patients with atrial fibrillation with use of anticoagulants, antiarrhythmic drugs, indications for performing of radiofrequency ablation and results of studies concerning long-term efficacy of such procedure are demonstrated. The discussion on the management of the patients in cases of sinus rhythm restoration or maintenance failure is described.

scholarly journals Mitral Valve Abnormalities Identified by Cardiovascular Magnetic Resonance Represent a Primary Phenotypic Expression of Hypertrophic Cardiomyopathy

Circulation ◽  
2011 ◽  
Vol 124 (1) ◽  
pp. 40-47 ◽  
Author(s):  
Martin S. Maron ◽  
Iacopo Olivotto ◽  
Caitlin Harrigan ◽  
Evan Appelbaum ◽  
C. Michael Gibson ◽  
...  
Keyword(s):  
Cardiovascular Magnetic Resonance ◽  
Hypertrophic Cardiomyopathy ◽  
Magnetic Resonance ◽  
Mitral Valve ◽  
Phenotypic Expression

Abstract 13296: Risk Loci of Hypertrophic Cardiomyopathy Identified via the UK Biobank

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Alex Gyftopoulos ◽  
Yi-Ju Chen ◽  
Libin Wang ◽  
Charles H Williams ◽  
Young Wook Chun ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Large Population ◽  
Phenotypic Expression ◽  
Coiled Coil ◽  
Intraflagellar Transport ◽  
Genetic Profile ◽  
Uk Biobank ◽  
Disease Manifestation ◽  
Pathogenic Variants ◽  
The Uk

Introduction: Hypertrophic cardiomyopathy (HCM) is the most commonly inherited cardiac disease affecting 1:500 to 1:200 individuals worldwide. HCM has a heterogeneous genetic profile and phenotypic expression. More than 1400 known pathogenic variants have been identified in 11 sarcomere genes. In about 40% of HCM patients, the genetic cause may not be identified. The same mutation may lead to different phenotypes and severity in different individuals. Identification of novel HCM genes and modifiers will expand our understanding of the signaling pathways that are responsible for phenotypic expression of HCM. Methods: The UK Biobank comprises clinical and genetic data for greater than 500,000 individuals. We used OASIS, an information system for analyzing, searching, and visualizing associations between phenotype and genotype data to analyze this data. We compared control individuals to HCM individuals identified by ICD-10 code (I42.1 and I42.2) in a 20-to-1 fashion. Related individuals and those with confounding diagnoses were excluded. Results: The analysis was performed with Plink’s GLM option, and we identified 84 variants with a minor allele frequency of 0.5% or greater in 65 genes associated with HCM with a p < 1x10 -6 , including 4 with p < 5x10 -8 . The identified genes encode lncRNAs, miRNAs, and membrane proteins. Variants with high significance were identified in the genes encoding putative ciliary components DNAL4 (dynein axonemal light chain 4; p = 2.9x10 -8 ), MYO1D (unconventional myosin 1D; p = 3.1x10 -8 ), ITFAP (intraflagellar transport associated protein; p = 9.5x10 -8 ), CABCOCO1 (ciliary associated calcium biding coiled-coil 1; p = 3.7x 10 -7 ), EVL (Enah-Vasp-like; p = 4.4x 10 -7 ) and IFT122 (intraflagellar transport 122; p = 8.0 x10 -7 ). Conclusion: While none of these have previously associated with HCM, our findings suggest ciliary structure and function may play a role in disease manifestation. Our method is unique by pooling individuals in a large population set to identify potential causative or contributing mutations. Bioinformatic tools, such as OASIS, allow for the identification of previously unrecognized variants that may play a role in the development of HCM. This approach has identified numerous novel genes as possible risk loci.

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