Clinical application of targeted next‐generation sequencing in fetuses with congenital heart defect

Hu, Ping; Qiao, Fengxiang; Wang, Yishuang; Meng, Lü; Ji, Xiuqing; Luo, Chen; Xu, Tianhua; Zhou, Ran; Zhang, J.; Yu, Bin; Wang, L.; Wang, T.; Pan, Qiong; Ma, Dong‐Lai; Liu, Dong; Xu, Zhengfeng

doi:10.1002/uog.19042

Cited by 43 publications

(53 citation statements)

References 30 publications

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“…Single‐gene disorders also contribute to CHD in both isolated and syndromic cases. For isolated CHDs an ever‐expanding list of genes is being identified that are directly or indirectly involved in cardiac morphogenesis . Occasionally, genes involved in syndromic CHD can also produce isolated malformations .…”

Section: Other Genetic Syndromes Associated With Cardiac Anomaliesmentioning

confidence: 99%

“…Recently, Hu et al customized a gene panel utilizing NGS to target 77 CHD‐related genes . Evaluation of 44 amniotic fluids from fetuses with sporadic CHD without chromosomal abnormalities identified 13.6% (n = 6/44) pathogenic variants (CHD7, CITED2, ZFPM2, MYH6, KMT2D, JAG).…”

Section: Other Genetic Syndromes Associated With Cardiac Anomaliesmentioning

confidence: 99%

“…Evaluation of 44 amniotic fluids from fetuses with sporadic CHD without chromosomal abnormalities identified 13.6% (n = 6/44) pathogenic variants (CHD7, CITED2, ZFPM2, MYH6, KMT2D, JAG). Over half (4/6) of the pathogenic variants were in genes associated with syndromic CHD, although no other features were detected on prenatal ultrasound …”

Section: Other Genetic Syndromes Associated With Cardiac Anomaliesmentioning

confidence: 99%

“…For isolated CHDs an ever-expanding list of genes is being identified that are directly or indirectly involved in cardiac morphogenesis. 87,88 Occasionally, genes involved in syndromic CHD can also produce isolated malformations. 8 Although nonsyndromic cases are thought to have a multifactorial origin, rare families with Mendelian inheritance have been described.…”

Section: Single-gene Disordersmentioning

confidence: 99%

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Fetal cardiac abnormalities: Genetic etiologies to be considered

et al. 2019

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Congenital heart diseases are a common prenatal finding. The prenatal identification of an associated genetic syndrome or a major extracardiac anomaly helps to understand the etiopathogenic diagnosis. Besides, it also assesses the prognosis, management, and familial recurrence risk while strongly influences parental decision to choose termination of pregnancy or postnatal care. This review article describes the most common genetic diagnoses associated with a prenatal finding of a congenital heart disease and a suggested diagnostic process.

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Section: Other Genetic Syndromes Associated With Cardiac Anomaliesmentioning

confidence: 99%

Section: Other Genetic Syndromes Associated With Cardiac Anomaliesmentioning

confidence: 99%

Section: Other Genetic Syndromes Associated With Cardiac Anomaliesmentioning

confidence: 99%

Section: Single-gene Disordersmentioning

confidence: 99%

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Fetal cardiac abnormalities: Genetic etiologies to be considered

et al. 2019

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“…The H3K4 methyltransferase KMT2D (MIM 602113)also known as ALR, MLL4, or sometimes MLL2-has been shown to be mutated in patients with congenital heart disease. 1,[5][6][7][8] KMT2D is a large protein with over 5500 amino acids and harbors a C-terminal SET domain, required for H3K4 methyltransferase activity. KMT2D has been shown to catalyze H3K4 mono-, di-or tri-methylation.…”

Section: Introductionmentioning

confidence: 99%

Loss of function of Kmt2d, a gene mutated in Kabuki syndrome, affects heart development in Xenopus laevis

Schwenty-Lara

Nürnberger

Borchers

2019

Developmental Dynamics

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Background Kabuki syndrome is a haploinsufficient congenital multi‐organ malformation syndrome, which frequently includes severe heart defects. Mutations in the histone H3K4 methyltransferase KMT2D have been identified as the main cause of Kabuki syndrome, however, the role of KMT2D in heart development remains to be characterized. Results Here we analyze the function of Kmt2d at different stages of Xenopus heart development. Xenopus Kmt2d is ubiquitously expressed at early stages of cardiogenesis, with enrichment in the anterior region including the cardiac precursor cells. Morpholino‐mediated knockdown of Kmt2d led to hypoplastic hearts lacking the three‐chambered structure. Analyzing different stages of cardiogenesis revealed that development of the first and second heart fields as well as cardiac differentiation were severely affected by loss of Kmt2d function. Conclusion Kmt2d loss of function in Xenopus recapitulates the hypoplastic heart defects observed in Kabuki syndrome patients and shows that Kmt2d function is required for the establishment of the primary and secondary heart fields. Thus, Xenopus Kmt2d morphants can be a valuable tool to elucidate the etiology of the congenital heart defects associated with Kabuki syndrome.

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