Congenital valvular defects associated with deleterious mutations in the<i>PLD1</i>gene

Ta‐Shma, Asaf; Zhang, Kai; Salimova, Ekaterina; Zernecke, Alma; Sieiro-Mosti, Daniel; Stegner, David; Furtado, Milena B.; Shaag, Avraham; Perles, Zeev; Nieswandt, Bernhard; Rein, Azaria J.J.T.; Rosenthal, Nadia; Neiman, Aaron M.; Elpeleg, Orly

doi:10.1136/jmedgenet-2016-104259

Cited by 40 publications

(34 citation statements)

References 34 publications

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“…Sequences were determined by HiSeq2000 (Illumina, San Diego, CA, USA). The full sequencing methodology and variant interpretation protocol were previously described (Ta-Shma et al 2017). Following reads alignment to human genome (hg19), variant calling and filtration, all remaining variants were heterozygous, and there were no variants in any of the genes of the Clinical Genomic Database (CGD) that could fit an Xlinked or autosomal recessive or dominant mode of inheritance (Solomon et al 2013).…”

Section: Resultsmentioning

confidence: 99%

Inherited SHQ1 mutations impair interaction with NAP57/dyskerin, a major target in dyskeratosis congenita

Bizarro

Meier

2017

Molec Gen & Gen Med

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BackgroundThe inherited bone marrow failure syndrome dyskeratosis congenita (DC) is most frequently caused by mutations in DKC1 (MIM# 300126), the gene encoding NAP57 (aka dyskerin). The typically missense mutations modulate the interaction of NAP57 with its chaperone SHQ1, but no DC mutations have been identified in SHQ1 (MIM# 613663). Here, we report on two compound heterozygous mutations in SHQ1 in a patient with a severe neurological disorder including cerebellar degeneration.MethodsThe SHQ1 mutations were identified by patient exome sequencing. The impact of the mutations was assessed in pulldown assays with recombinant NAP57.ResultsThe SHQ1 mutations were the only set of mutations consistent with an autosomal recessive mode of inheritance. The mutations map to the SHQ1‐NAP57 interface and impair the interaction of the recombinant SHQ1 variants with NAP57.ConclusionIntrauterine growth retardation and the neurological phenotype of the patient are reminiscent of the severe clinical variant of DC, the Hoyeraal‐Hreidarsson syndrome (HH). Hence, SHQ1 screening may be warranted in patients with inherited bone marrow failure syndromes.

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Section: Resultsmentioning

confidence: 99%

Inherited SHQ1 mutations impair interaction with NAP57/dyskerin, a major target in dyskeratosis congenita

Bizarro

Meier

2017

Molec Gen & Gen Med

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“…Variant interpretation protocol has been previously described. 5 WES of affected individual 5 and her parents and affected individual 6 was performed on exon targets captured using SureSelect Human All Exon 50 Mb Kit V.4 (Agilent Technologies, Santa Clara, CA, USA). Sequences were determined by HiSeq2000 (Illumina, San Diego, CA, USA).…”

mentioning

confidence: 99%

“…The full sequencing methodology and variant interpretation protocol were previously described. 5 Clinical exome sequencing of affected individual 7 and her parents was performed at Ambry Genetics as previously described. 6 All the procedures were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national); proper informed consent was obtained from all guardians.…”

mentioning

confidence: 99%

Heterozygous De Novo UBTF Gain-of-Function Variant Is Associated with Neurodegeneration in Childhood

Edvardson

Nicolae

Agrawal

et al. 2017

The American Journal of Human Genetics

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“…In the past years, several genetic studies were also performed in patients with familial MR due to MVP and identified three possible loci for autosomal-dominant MVP on chromosomes 16 (MMVP1), 11 (MMVP2) and 13 (MMVP3). [13][14][15] Furthermore, DCHS1 and PLD1 have been linked to autosomal MVP 16,17 and mutations in the filamin A (FLNA) gene have been identified to cause a X-linked form of MVP. 18 In line with these findings, the present study observed different distributions of affected family members between families (Figure 3).…”

Section: Heritability Of Mvp and Mrmentioning

confidence: 99%

Familial occurrence of mitral regurgitation in patients with mitral valve prolapse undergoing mitral valve surgery

Hiemstra

Wijngaarden

Bos

et al. 2020

European Journal of Preventive Cardiology

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Background: Initial studies have suggested the familial clustering of mitral valve prolapse, but most of them were either community based among unselected individuals or applied non-specific diagnostic criteria. Therefore little is known about the familial distribution of mitral regurgitation in a referral-type population with a more severe mitral valve prolapse phenotype. The objective of this study was to evaluate the presence of familial mitral regurgitation in patients undergoing surgery for mitral valve prolapse, differentiating patients with Barlow's disease, Barlow forme fruste and fibro-elastic deficiency. Methods: A total of 385 patients (62 AE 12 years, 63% men) who underwent surgery for mitral valve prolapse were contacted to assess cardiac family history systematically. Only the documented presence of mitral regurgitation was considered to define 'familial mitral regurgitation'. In the probands, the aetiology of mitral valve prolapse was defined by surgical observations. Results: A total of 107 (28%) probands were classified as having Barlow's disease, 85 (22%) as Barlow forme fruste and 193 (50%) patients as fibro-elastic deficiency. In total, 51 patients (13%) reported a clear family history for mitral regurgitation; these patients were significantly younger, more often diagnosed with Barlow's disease and also reported more sudden death in their family as compared with 'sporadic mitral regurgitation'. In particular, 'familial mitral regurgitation' was reported in 28 patients with Barlow's disease (26%), 15 patients (8%) with fibro-elastic deficiency and eight (9%) with Barlow forme fruste (P < 0.001). Conclusions: In a large cohort of patients operated for mitral valve prolapse, the self-reported prevalence of familial mitral regurgitation was 26% in patients with Barlow's disease and still 8% in patients with fibro-elastic deficiency, highlighting the importance of familial anamnesis and echocardiographic screening in all mitral valve prolapse patients.

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Congenital valvular defects associated with deleterious mutations in thePLD1gene

Abstract: The findings support a role for PLD1 in normal heart valvulogenesis.

Cited by 40 publications

References 34 publications

Inherited SHQ1 mutations impair interaction with NAP57/dyskerin, a major target in dyskeratosis congenita

Inherited SHQ1 mutations impair interaction with NAP57/dyskerin, a major target in dyskeratosis congenita

Heterozygous De Novo UBTF Gain-of-Function Variant Is Associated with Neurodegeneration in Childhood

Familial occurrence of mitral regurgitation in patients with mitral valve prolapse undergoing mitral valve surgery

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