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

Xiong, Ying; Hong, Xia; Yuan, Lamei; Deng, Sheng; Ding, Zerui; Deng, Hao

doi:10.1111/jcmm.16866

Cited by 8 publications

(5 citation statements)

References 58 publications

(162 reference statements)

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“…In vitro minigene splicing assays were performed as described previously [ 9 ] using an amplified sequence with the c.4342 + 5_4342 + 8delGTGA variant from a healthy control genome, and using the following primers (thus including exon 23, a portion of intron 23, exon 24, intron 24, and exon 25):…”

Section: Methodsmentioning

confidence: 99%

A novel intronic TCOF1 pathogenic variant in a Chinese family with Treacher Collins syndrome

Sun,

Xu,

Chen

et al. 2024

BMC Med Genomics

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Background Treacher Collins syndrome (TCS; OMIM 154500) is a craniofacial developmental disorder. Methods To investigate the genetic features of a four-generation Chinese family with TCS, clinical examinations, hearing tests, computed tomography, whole-exome sequencing (WES), Sanger sequencing, reverse transcription (RT)-PCR, and the Minigene assay were performed. Results The probands, an 11-year-old male and his cousin exhibited typical clinical manifestations of TCS including conductive hearing loss, downward slanting palpebral fissures, and mandibular hypoplasia. Computed tomography revealed bilateral fusion of the anterior and posterior stapedial crura and malformation of the long crura of the incus. WES of both patients revealed a novel heterozygous intronic variant, i.e., c.4342 + 5_4342 + 8delGTGA (NM_001371623.1) in TCOF1. Minigene expression analysis revealed that the c.4342 + 5_4342 + 8delGTGA variant in TCOF1 caused a partial deletion of exon 24 (c.4115_4342del: p.Gly1373_Arg1448del), which was predicted to yield a truncated protein. The deletion was further confirmed via RT-PCR and sequencing of DNA from proband blood cells. A heterozygous variant in the POLR1C gene (NM_203290; exon6; c.525delG) was found almost co-segregated with the TCOF1 pathogenic variant. Conclusions In conclusion, we identified a heterozygous TCOF1 splicing variant c.4342 + 5_4342 + 8delGTGA (splicing) in a Chinese TSC family with ossicular chain malformations and facial anomalies. Our findings broadened the spectrum of TCS variants and will facilitate diagnostics and prognostic predictions.

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Section: Methodsmentioning

confidence: 99%

A novel intronic TCOF1 pathogenic variant in a Chinese family with Treacher Collins syndrome

Sun,

Xu,

Chen

et al. 2024

BMC Med Genomics

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“…Whole exome sequencing (WES) was conducted on the proband and their parents of pedigree 1, and the proband of pedigree 2. Genomic DNA (gDNA) of participating individuals was extracted from peripheral venous blood lymphocytes following the manufacturer’s protocol ( Huang et al, 2021 ; Xiong et al, 2021 ). The qualified gDNA was fragmented randomly and then processed for end-repairing, A-tailing, and adaptor ligation.…”

Section: Methodsmentioning

confidence: 99%

Identification of COL4A4 variants in Chinese patients with familial hematuria

Gao

Yuan

et al. 2023

Front. Genet.

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Background: Benign familial hematuria and Alport syndrome are common causes of familial hematuria among children and young adults, which are attributable to variants in the collagen type IV alpha chain genes, COL4A3, COL4A4, or COL4A5. The study was conducted to identify the underlying genetic causes in patients with familial hematuria.Methods: Two unrelated Han-Chinese pedigrees with familial hematuria were recruited for this study. Whole exome sequencing was combined with in silico analysis to identify potential genetic variants, followed by variant confirmation by Sanger sequencing. Reverse transcription, PCR, and Sanger sequencing were performed to evaluate the effect of the detected splicing variant on mRNA splicing.Results: A novel heterozygous splicing c.595-1G>A variant and a known heterozygous c.1715G>C variant in the collagen type IV alpha 4 chain gene (COL4A4) were identified and confirmed in patients of pedigree 1 and pedigree 2, respectively. Complementary DNA analysis indicated this splicing variant could abolish the canonical splice acceptor site and cause a single nucleotide deletion of exon 10, which was predicted to produce a truncated protein.Conclusions: The two COL4A4 variants, c.595-1G>A variant and c.1715G>C (p.Gly572Ala) variant, were identified as the genetic etiologies of two families with familial hematuria, respectively. Our study broadened the variant spectrum of the COL4A4 gene and explained the possible pathogenesis, which will benefit clinical management and genetic counseling.

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“…The candidate variants were filtered by the following databases, including the 1000 Genomes Project, Single Nucleotide Polymorphism database (version 154), National Heart, Lung, and Blood Institute-Exome Sequencing Project 6500, Exome Aggregation Consortium, Genome Aggregation Database, China Metabolic Analytics Project, the Human Gene Mutation Database (HGMD), and ClinVar database. Variant pathogenicity was predicted by MutationTaster2021 ( https://www.genecascade.org/MutationTaster2021/ ), Protein Variation Effect Analyzer (PROVEAN, https://provean.jcvi.org/ ), the Sorting Intolerant from Tolerant (SIFT), the Polymorphism Phenotyping v2 (Polyphen-2, http://genetics.bwh.harvard.edu/pph2 ), and MutationAssessor ( http://mutationassessor.org/r3/ ) ( Xiang et al, 2019a ; Wu et al, 2021 ; Xiong et al, 2021 ; Yu et al, 2022 ).…”

Section: Methodsmentioning

confidence: 99%

Novel compound heterozygous variants in the USH2A gene associated with autosomal recessive retinitis pigmentosa without hearing loss

Huang

Yuan²,

He³

et al. 2023

Front. Cell Dev. Biol.

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Background: Retinitis pigmentosa (RP) is a group of progressive inherited retinal dystrophies characterized by the primary degeneration of rod photoreceptors and the subsequent loss of cone photoreceptors because of cell death. It is caused by different mechanisms, including inflammation, apoptosis, necroptosis, pyroptosis, and autophagy. Variants in the usherin gene (USH2A) have been reported in autosomal recessive RP with or without hearing loss. In the present study, we aimed to identify causative variants in a Han-Chinese pedigree with autosomal recessive RP.Methods: A six-member, three-generation Han-Chinese family with autosomal recessive RP was recruited. A full clinical examination, whole exome sequencing, and Sanger sequencing, as well as co-segregation analysis were performed.Results: Three heterozygous variants in the USH2A gene, c.3304C>T (p.Q1102*), c.4745T>C (p.L1582P), and c.14740G>A (p.E4914K), were identified in the proband, which were inherited from parents and transmitted to the daughters. Bioinformatics analysis supported the pathogenicity of the c.3304C>T (p.Q1102*) and c.4745T>C (p.L1582P) variants.Conclusions: Novel compound heterozygous variants in the USH2A gene, c.3304C>T (p.Q1102*) and c.4745T>C (p.L1582P), were identified as the genetic causes of autosomal recessive RP. The findings may enhance the current knowledge of the pathogenesis of USH2A-associated phenotypes, expand the spectrum of the USH2A gene variants, and contribute to improved genetic counseling, prenatal diagnosis, and disease management.

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

Cited by 8 publications

References 58 publications

A novel intronic TCOF1 pathogenic variant in a Chinese family with Treacher Collins syndrome

A novel intronic TCOF1 pathogenic variant in a Chinese family with Treacher Collins syndrome

Identification of COL4A4 variants in Chinese patients with familial hematuria

Novel compound heterozygous variants in the USH2A gene associated with autosomal recessive retinitis pigmentosa without hearing loss

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