An adult female with 5q34-q35.2 deletion: A rare syndromic presentation of left ventricular non-compaction and congenital heart disease

Arya, Priyanka; Wilson, Theodore E.; Parent, John J.; Ware, Stephanie M.; Breman, Amy M.; Helm, Benjamin M.

doi:10.1016/j.ejmg.2019.103797

Cited by 6 publications

(4 citation statements)

References 21 publications

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“…In vertebrates, all teneurins (1–4) show a gradient of expression in the thalamus, which putatively guides the axon termination from sensory neurons ( Tucker, 2018 ). Deletion of the region (5q34) reportedly results in mental retardation in humans ( Lee et al, 2016 ; Arya et al, 2020 ), which would point to an effect this region has on brain development. The results therefore suggest that altered sensory processing based on differential sensori-thalamic neural connectivity could subserve the association of misophonia with TENM2 variants.…”

Section: Discussionmentioning

confidence: 99%

A genome-wide association study of a rage-related misophonia symptom and the genetic link with audiological traits, psychiatric disorders, and personality

et al. 2023

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IntroductionPeople with misophonia experience strong negative emotional responses to sounds and associated stimuli—mostly human produced—to an extent that it may cause impairment in social functioning. The exact nature of the disorder remains a matter of ongoing research and debate. Here, we investigated the genetic etiology of misophonia to understand contributing genetic factors and shed light on individual differences in characteristics that are related to the disorder.MethodsFor misophonia, we used an unpublished genome-wide association study (GWAS) from genetic service provider 23andMe, Inc., on a self-report item probing a single common misophonic symptom: the occurrence of rage when others produce eating sounds. First, we used gene-based and functional annotation analyses to explore neurobiological determinants of the rage-related misophonia symptom. Next, we calculated genetic correlations (rG) of this rage-related misophonia symptom GWAS with a wide range of traits and disorders from audiology (tinnitus, hearing performance, and hearing trauma), psychiatry, neurology, and personality traits.ResultsThe rage-related misophonia symptom was significantly correlated with tinnitus, major depression disorder (MDD), post-traumatic stress disorder (PTSD), and generalized anxiety disorder (GAD; 0.12 < rG < 0.22). Stronger genetic correlations (0.21 < rG < 0.42) were observed for two clusters of personality traits: a guilt/neuroticism and an irritability/sensitivity cluster. Our results showed no genetic correlation with attention deficit and hyperactivity disorder, obsessive-compulsive disorder, and psychotic disorders. A negative correlation with autism spectrum disorder (ASD) was found, which may be surprising given the previously reported comorbidities and the sensory sensitivity reported in ASD. Clustering algorithms showed that rage-related misophonia consistently clustered with MDD, generalized anxiety, PTSD, and related personality traits.DiscussionWe conclude that—based on the genetics of a common misophonia symptom—misophonia most strongly clusters with psychiatric disorders and a personality profile consistent with anxiety and PTSD.

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Section: Discussionmentioning

confidence: 99%

A genome-wide association study of a rage-related misophonia symptom and the genetic link with audiological traits, psychiatric disorders, and personality

et al. 2023

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“…Cardiac manifestations mostly include septal defects and cardiac conduction disease, such as bradycardia, bundle branch block, and atrial fibrillation (Ross et al, 2018). (NKX2‐5 and TBX5 variants have been recently associated to LVNC (Arya et al, 2019; Ross et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…(NKX2-5 and TBX5 variants have been recently associated to LVNC (Arya et al, 2019;Ross et al, 2020).…”

Section: The Role Of Gata4 In Cardiac Development and Ventricular Fun...mentioning

confidence: 99%

8p23.1 deletion: Look out for left ventricular hypertrabeculation and not only congenital heart diseases. Single‐center experience and literature revision

Cicenia

Alesi

Orlando

et al. 2021

American J of Med Genetics Pt A

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Deletions involving the distal portion of the short arm of chromosome 8(8p23.1) show a high phenotypic variability. Congenital heart diseases (CHD) are often described. GATA4 when mutated or deleted is reported to be involved in cardiac morphogenesis. Only twice, left ventricular non compaction (LVNC) was reported in literature in association with 8p23.1 deletion. The present cohort includes five new patients with 8p23.1 deletions including GATA4. The spectrum of CHD is variable. Moreover, in four patients, LV hypertrabeculation was detected and in the fifth LVNC was recognized. Literature revision identified 45 patients with 8p23.1 deletions (encompassing GATA4) and heart involvement. It included wide spectrum of CHD including: heterotaxy spectrum 7/45 (15, 6%), atrioventricular canal 14/45 (balanced 3/45 including two of them with hypoplastic aortic arch; unbalanced 4/45, Fallot-AVC 1/45, partial AVC 3/45, unspecified 3/45), predominant major left heart lesions included 2/45 (4, 4%): interrupted aortic arch and hypoplastic left heart syndrome. Left ventricular hypertrabeculation might be potentially underestimated in patients with 8p23.1 deletion. These might suggest the importance of including microarray analysis in this group of patients. Moreover, 8p23.1 microdeletion or GATA4 variants can be considered in heterotaxy genetic panels.

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“…Significant familial aggregation of CHD has been reported, with the risk of CHD recurrence in the first-degree offspring of an affected parent being between 3 and 19% depending on the distinct types of lesion ( 55 ). In addition to chromosomal alterations encompassing aneuploidies, microdeletions and microduplications, pathogenetic variations in >100 genes amply expressed in the developing heart, encompassing those encoding sarcomeric proteins, transcription factors, chromatin modifies and signal-transducing molecules, have been determined to contribute to CHD ( 1 , 2 , 52 , 53 , 56-83 ). Of these reported CHD-causative genes, the majority code for cardiac core transcription factors, such as T-box transcription factor (TBX)1, TBX20, TBX5, NK2 homeobox 5, GATA binding protein (GATA)6, GATA4, GATA5, heart and neural crest derivatives expressed (HAND)1 and HAND2( 84 ).…”

Section: Introductionmentioning

confidence: 99%

A novel KLF13 mutation underlying congenital patent ductus arteriosus and ventricular septal defect, as well as bicuspid aortic valve

et al. 2022

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Recently, mutations in the Kruppel-like factor 13 (KLF13) gene encoding a Kruppel-like transcription factor have been reported to cause congenital heart disease (CHD). However, due to pronounced genetic heterogeneity, the mutational spectrum of KLF13 in other cohorts of cases suffering from distinct types of CHD remain to be ascertained. In the present investigation, by Sanger sequencing of KLF13 in 316 unrelated cases affected by different forms of CHD, a new mutation in heterozygous status, NM_015995.3: c.430G>T; p.(Glu144*), was detected in an index patient affected with patent ductus arteriosus (PDA) and ventricular septal defect (VSD), as well as bicuspid aortic valve (BAV), with a mutation frequency of ~0.32%. Genetic investigation of the available family members of the proband demonstrated that the truncating mutation co-segregated with CHD. The nonsense mutation was not observed in 400 unrelated volunteers without CHD who were enrolled as control subjects. Quantitative biological measurements with dual luciferase reporters revealed that Glu144*-mutant KLF13 did not transactivate the downstream genes vascular endothelial growth factor A and natriuretic peptide A. In addition, the mutation abrogated the synergistic transcriptional activation between KLF13 and T-box transcription factor 5, a well-established CHD-causing gene. In conclusion, the present study indicates that genetically defective KLF13 contributes to familial PDA and VSD, as well as BAV, which expands the phenotypic spectrum linked to KLF13, and reveals a novel molecular pathogenesis of the disease, providing a new molecular target for the early prophylaxis and individualized treatment of CHD.

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An adult female with 5q34-q35.2 deletion: A rare syndromic presentation of left ventricular non-compaction and congenital heart disease

Cited by 6 publications

References 21 publications

A genome-wide association study of a rage-related misophonia symptom and the genetic link with audiological traits, psychiatric disorders, and personality

A genome-wide association study of a rage-related misophonia symptom and the genetic link with audiological traits, psychiatric disorders, and personality

8p23.1 deletion: Look out for left ventricular hypertrabeculation and not only congenital heart diseases. Single‐center experience and literature revision

A novel KLF13 mutation underlying congenital patent ductus arteriosus and ventricular septal defect, as well as bicuspid aortic valve

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