Identification of a frame shift mutation in the <i>CCDC151</i> gene in a Han-Chinese family with Kartagener syndrome

Deng, Sheng; Wu, Shan; Hong, Xia; Wang, Xiong; Deng, Xiong; Liao, Junxi; Deng, Hao; Yuan, Lamei

doi:10.1042/bsr20192510

Cited by 11 publications

(8 citation statements)

References 68 publications

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“…Exome sequencing, a cost-saving measure, has been used in the genetic investigation of HTX [12][13][14]. Our previous study has successfully identified pathogenic variants in two Chinese families with SI phenotype via exome sequencing [15,16]. In this study, exome sequencing and Sanger sequencing detected the compound heterozygous variants, c.3426-1G>A and c.4306C>T (p. (Arg1436Trp)), in the dynein axonemal heavy chain 11 gene (DNAH11, NM_001277115.1) in a Han Chinese family with HTX and CHD.…”

Section: Introductionmentioning

confidence: 99%

DNAH11 compound heterozygous variants cause heterotaxy and congenital heart disease

et al. 2021

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Heterotaxy (HTX), a condition characterized by internal organs not being arranged as expected relative to each other and to the left-right axis, is often accompanied with congenital heart disease (CHD). The purpose was to detect the pathogenic variants in a Chinese family with HTX and CHD. A non-consanguineous Han Chinese family with HTX and CHD, and 200 unrelated healthy subjects were enlisted. Exome sequencing and Sanger sequencing were applied to identify the genetic basis of the HTX family. Compound heterozygous variants, c.3426-1G>A and c.4306C>T (p.(Arg1436Trp)), in the dynein axonemal heavy chain 11 gene (DNAH11) were identified in the proband via exome sequencing and further confirmed by Sanger sequencing. Neither c.3426-1G>A nor c.4306C>T variant in the DNAH11 gene was detected in 200 healthy controls. The DNAH11 c.3426-1G>A variant was predicted as altering the acceptor splice site and most likely affecting splicing. The DNAH11 c.4306C>T variant was predicted to be damaging, which may reduce the phenotype severity. The compound heterozygous variants, c.3426-1G>A and c.4306C>T, in the DNAH11 gene might be the pathogenic alterations resulting in HTX and CHD in this family. These findings broaden the variant spectrum of the DNAH11 gene and increase knowledge used in genetic counseling for the HTX family.

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Section: Introductionmentioning

confidence: 99%

DNAH11 compound heterozygous variants cause heterotaxy and congenital heart disease

et al. 2021

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“…To date, a total of seven likely loss-of-function variants in ODAD3 have been reported in PCD (Supplementary Table 2). The reported ODAD3 variants including three non-sense variants: p.(Gly309 * ) (Hjeij et al, 2014); p.(Ser409 * ) (Hjeij et al, 2014); p.(Glu109 * ) (Zhang et al, 2019); three frame-shifting variants: p.(Gly56Aspfs * 26) (Deng et al, 2020); p.(Lys77Leufs * 6) (Mani et al, 2020); p.(His199Argfs * 60) (Olm et al, 2019) and one splice site variant: c.244+1G>A (Monies et al, 2019). The only two hitherto reported female patients (10 week and 1 year-old, respectively) did not reach reproductive age.…”

Section: Discussionmentioning

confidence: 99%

Case Report: Identification of a Novel ODAD3 Variant in a Patient With Primary Ciliary Dyskinesia

et al. 2021

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Background:ODAD3 encodes a protein of 595 amino acids and contain three highly conserved coiled-coil domains, which is essential for cilia axoneme dynein arm assembly and docking. Primary ciliary dyskinesia (PCD) of ODAD3 deficiency are rarely reported. Female infertility in PCD related to ODAD3 variants has not been reported.Methods: Whole-exome and Sanger sequencing were used to identify the disease-related gene of the patient with PCD in a consanguineous Chinese family. Domain analysis was applied to predict the impact of the variant on ODAD3 protein.Results: The 35 year-old female patient exhibited chronic sinusitis, diffuse bronchiectasis, dextrocardia and infertility. We identified a novel homozygous variant in ODAD3, c.1166_1169dupAGAC, p.(Leu391Aspfs*105) in the PCD patient by exome sequencing and Sanger sequencing. This frameshift variant was predicted to be disease causing by bioinformatics analysis and was also not presented in the current authorized large genetic databases.Conclusions: Our study enriches the genetic spectrum and clinical phenotypes of ODAD3 variants in PCD and provide more evidence for future genetic counseling and gene-targeted therapy for this disease.

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“…DNA nanoballs were formed via rolling circle amplification using circular single‐stranded libraries and then loaded onto a sequencing chip. The captured exome library underwent high‐throughput sequencing on the BGISEQ‐500 (BGI, Shenzhen, China) platform in accord with the manufacturer's instructions 24 . Sequencing‐derived raw image files obtained were transformed into ‘raw data’ with BGISEQ‐500 base calling software.…”

Section: Methodsmentioning

confidence: 99%

“…After excluding synonymous variants, non‐exonic SNPs and non‐canonical splicing sites, non‐synonymous variants in the 42 PCD‐associated genes were selected 26 http://www.mutationtaster.org/), Sorting Intolerant from Tolerant (SIFT, http://sift.jcvi.org/), Polymorphism Phenotyping version 2 (PolyPhen‐2, http://genetics.bwh.harvard.edu/pph2/) and Berkeley Drosophila Genome Project/Splice Site Prediction by Neural Network (BDGP/NNSplice, http://www.fruitfly.org/seq_tools/splice.html 24 . Sanger sequencing of enrolled family members verified the identified potential causative variants with an ABI3500 sequencer (Applied Biosystems Inc.).…”

Section: Methodsmentioning

confidence: 99%

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Identification of compound heterozygous DNAH11 variants in a Han‐Chinese family with primary ciliary dyskinesia

Xiong

Hong

Yuan

et al. 2021

J Cellular Molecular Medi

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Primary ciliary dyskinesia (PCD) is a group of genetically and clinically heterogeneous disorders with motile cilia dysfunction. It is clinically characterized by oto‐sino‐pulmonary diseases and subfertility, and half of the patients have situs inversus (Kartagener syndrome). To identify the genetic cause in a Han‐Chinese pedigree, whole‐exome sequencing was conducted in the 37‐year‐old proband, and then, Sanger sequencing was performed on available family members. Minigene splicing assay was applied to verify the impact of the splice‐site variant. Compound heterozygous variants including a splice‐site variant (c.1974‐1G>C, rs1359107415) and a missense variant (c.7787G>A, p.(Arg2596Gln), rs780492669), in the dynein axonemal heavy chain 11 gene (DNAH11) were identified and confirmed as the disease‐associated variants of this lineage. The minigene expression in vitro revealed that the c.1974‐1G>C variant could cause skipping over exon 12, predicted to result in a truncated protein. This discovery may enlarge the DNAH11 variant spectrum of PCD, promote accurate genetic counselling and contribute to PCD diagnosis.

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Identification of a frame shift mutation in the CCDC151 gene in a Han-Chinese family with Kartagener syndrome

Cited by 11 publications

References 68 publications

DNAH11 compound heterozygous variants cause heterotaxy and congenital heart disease

DNAH11 compound heterozygous variants cause heterotaxy and congenital heart disease

Case Report: Identification of a Novel ODAD3 Variant in a Patient With Primary Ciliary Dyskinesia

Identification of compound heterozygous DNAH11 variants in a Han‐Chinese family with primary ciliary dyskinesia

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