Case Report: Identification of Maternal Low-Level Mosaicism in the Dystrophin Gene by Droplet Digital Polymerase Chain Reaction

Jin, Pengzhen; Gao, Xiaotong; Wang, Miaomiao; Qian, Yeqing; Yang, Jingjin; Yang, Yanmei; Xu, Yuqing; Xu, Yanfei; Dong, Minyue

doi:10.3389/fgene.2021.686993

Cited by 5 publications

(5 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This showed that ultra-deep sequencing, as an approach for the diagnosis of low-level mosaic variations, could significantly increase the positive rate of diagnosis. However, as an absolute quantitative method with greater precision and sensitivity, ddPCR could be a promising technique for detection of mosaicism, especially for asymptomatic carriers who suffer from recurrent occurrence (Jin et al, 2021). Jin et al (2020) reported a case of tuberous sclerosis (TSC) with atypical clinical symptoms.…”

Section: Discussionmentioning

confidence: 99%

“…However, as an absolute quantitative method with greater precision and sensitivity, ddPCR could be a promising technique for detection of mosaicism, especially for asymptomatic carriers who suffer from recurrent occurrence (Jin et al, 2021 ). Jin et al ( 2020 ) reported a case of tuberous sclerosis (TSC) with atypical clinical symptoms.…”

Section: Discussionmentioning

confidence: 99%

“…The ddPCR system quantifies the number of positive and negative signal droplets and the absolute amount of the target genomic region of interest could be counted precisely (Fujiki et al, 2016 ). It has been reported that ddPCR can quantitatively detect mutations with a sensitivity below 0.001%, which indicates that ddPCR could be a reliable approach to identify low‐level mosaicism (Jin et al, 2021 ; Postel et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Detection of gonosomal mosaicism by ultra‐deep sequencing and droplet digital PCR in patients with Emery–Dreifuss muscular dystrophy

Xie

Luo

Zhong

et al. 2023

Molec Gen & Gen Med

View full text Add to dashboard Cite

Background Emery–Dreifuss muscular dystrophy (EDMD2) is a rare form of muscular dystrophy that is inherited as an autosomal dominant trait. In some patients, it is inherited from parental mosaicism, and this increases the recurrence risk significantly. The presence of mosaicism is underestimated due to the limitations of genetic testing and the difficulty in obtaining samples. Methods A peripheral blood sample from a 9‐year‐old girl with EDMD2 was analyzed by enhanced whole exome sequencing (WES). Sanger sequencing in her unaffected parents and younger sister was performed for validation. In the mother, ultra‐deep sequencing and droplet digital PCR (ddPCR) in multiple samples (blood, urine, saliva, oral epithelium, and nail clippings) were performed in order to identify the suspected mosaicism of the variant. Results WES revealed a heterozygous mutation (LMNA, c.1622G>A) in the proband. Sanger sequencing of the mother suggested the presence of mosaicism. The ratio of mosaic mutation was confirmed in different samples by ultra‐deep sequencing and ddPCR (19.98%–28.61% and 17.94%–28.33%, respectively). This inferred that the mosaic mutation may have occurred early during embryonic development and that the mother had gonosomal mosaicism. Conclusion We described a case of EDMD2 caused by maternal gonosomal mosaicism which was confirmed by using ultra‐deep sequencing and ddPCR. This study illustrates the importance of a systematic and comprehensive screening of parental mosaicism with more sensitive approaches and the use of multiple tissue samples.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Detection of gonosomal mosaicism by ultra‐deep sequencing and droplet digital PCR in patients with Emery–Dreifuss muscular dystrophy

Xie

Luo

Zhong

et al. 2023

Molec Gen & Gen Med

View full text Add to dashboard Cite

show abstract

“…Fetal amniocytes were cultured, and GTG-banding was performed according to standard cytogenetic procedures, yielding a 320–400 band level with a resolution of around 10 Mb. Generally, 30 metaphases were counted, and 5 metaphases were analyzed ( Jin et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Case Report: Prenatal diagnosis of fetal tetrasomy 9p initially identified by non-invasive prenatal testing

Chen²,

Chen³

et al. 2022

Front. Genet.

Self Cite

View full text Add to dashboard Cite

Tetrasomy 9p is a rare syndrome characterized by fetal growth restriction, Dandy-Walker malformation, cardiac anomalies, and facial abnormalities and is discovered by ultrasound during the prenatal examination. Herein, we report a fetus of tetrasomy 9p without obvious phenotypic manifestations during the first trimester that was identified by non-invasive prenatal testing (NIPT). NIPT revealed that the gain of 9p24.3–9p11 that was approximately 46.36 Mb in size. Karyotyping of amniocytes indicated an additional marker in all metaphase. Chromosome microarray and fluorescence in situ hybridization on uncultured amniocytes revealed tetrasomic of 9p24.3q13, and that the supernumerary chromosome is a dicentric isochromosome consisted of two copies of the 9p arm. Taken together, it was indicated that the fetal karyotype was 47,XY,+idic (9) (q13), and that multiple techniques are crucial to the prenatal diagnosis.

show abstract

“…Third-generation PCR has multiple applications. Some examples are viral quantification [60], oncology and haematology [61], and noninvasive prenatal diagnosis (NIPD) [62].…”

Section: D-pcrmentioning

confidence: 99%

Narrative Review: Update on the Molecular Diagnosis of Fragile X Syndrome

Ciobanu

Nucă

Popescu

et al. 2023

IJMS

View full text Add to dashboard Cite

The diagnosis and management of fragile X syndrome (FXS) have significantly improved in the last three decades, although the current diagnostic techniques are not yet able to precisely identify the number of repeats, methylation status, level of mosaicism, and/or the presence of AGG interruptions. A high number of repeats (>200) in the fragile X messenger ribonucleoprotein 1 gene (FMR1) results in hypermethylation of promoter and gene silencing. The actual molecular diagnosis is performed using a Southern blot, TP-PCR (Triplet-Repeat PCR), MS-PCR (Methylation-Specific PCR), and MS-MLPA (Methylation-Specific MLPA) with some limitations, with multiple assays being necessary to completely characterise a patient with FXS. The actual gold standard diagnosis uses Southern blot; however, it cannot accurately characterise all cases. Optical genome mapping is a new technology that has also been developed to approach the diagnosis of fragile X syndrome. Long-range sequencing represented by PacBio and Oxford Nanopore has the potential to replace the actual diagnosis and offers a complete characterization of molecular profiles in a single test. The new technologies have improved the diagnosis of fragile X syndrome and revealed unknown aberrations, but they are a long way from being used routinely in clinical practice.

show abstract

Case Report: Identification of Maternal Low-Level Mosaicism in the Dystrophin Gene by Droplet Digital Polymerase Chain Reaction

Cited by 5 publications

References 33 publications

Detection of gonosomal mosaicism by ultra‐deep sequencing and droplet digital PCR in patients with Emery–Dreifuss muscular dystrophy

Detection of gonosomal mosaicism by ultra‐deep sequencing and droplet digital PCR in patients with Emery–Dreifuss muscular dystrophy

Case Report: Prenatal diagnosis of fetal tetrasomy 9p initially identified by non-invasive prenatal testing

Narrative Review: Update on the Molecular Diagnosis of Fragile X Syndrome

Contact Info

Product

Resources

About