Prenatal diagnosis for a Chinese family with a de novo DMD gene mutation

Abstracts Background Duchenne muscular dystrophies (DMDs) are X-linked recessive neuromuscular disorders with malfunction or absence of the Dystrophin protein. Precise genetic diagnosis is critical for proper planning of patient care and treatment. In this study, we described a Chinese family with mosaic DMD mutations and discussed the best method for prenatal diagnosis and genetic counseling of X-linked familial disorders. Methods We investigated all variants of the whole dystrophin gene using multiple DNA samples isolated from the affected family and identified two variants of the DMD gene in a sick boy and two female carriers by targeted next generation sequencing (TNGS), Sanger sequencing, and haplotype analysis. Results We identified the hemizygous mutation c.6794delG (p.G2265Efs*6) of DMD in the sick boy, which was inherited from his mother. Unexpectedly, a novel heterozygous mutation c.6796delA (p.I2266Ffs*5) of the same gene, which was considered to be a de novo variant, was detected from his younger sister instead of his mother by Sanger sequencing. However, further NGS analysis of the mother and her amniotic fluid samples revealed that the mother carried a low-level mosaic c.6796delA mutation. Conclusions We reported two different mutations of the DMD gene in two siblings, including the novel mutation c.6796delA (p.I2266Ffs*5) inherited from the asymptomatic mosaic-carrier mother. This finding has enriched the knowledge of the pathogenesis of DMD. If no mutation is detected in obligate carriers, the administration of intricate STR/NGS/Sanger analysis will provide new ideas on the prenatal diagnosis of DMD.

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Prenatal Diagnosis of Twin Fetuses with a Novel AR Gene Mutation in a Chinese Family of Complete Androgen Insensitivity Syndrome

Fetal and Pediatric Pathology ◽

10.1080/15513815.2017.1332120 ◽

2017 ◽

Vol 36 (6) ◽

pp. 432-436

Author(s):

Weiqing Wu ◽

Qian Geng ◽

Yang Liu ◽

Zhiyong Xu ◽

Peining Li ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Gene Mutation ◽

Androgen Insensitivity Syndrome ◽

Chinese Family ◽

Complete Androgen Insensitivity Syndrome ◽

Androgen Insensitivity

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DMD/BMD prenatal diagnosis and treatment expectation in a single centre in China for 15 years

BMC Medical Genomics ◽

10.1186/s12920-021-01024-8 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Xingjian Zhong ◽

Siying Cui ◽

Lina Liu ◽

Yuxia Yang ◽

Xiangdong Kong

Keyword(s):

Prenatal Diagnosis ◽

De Novo ◽

Treatment Method ◽

Single Centre ◽

Muscular Disease ◽

History Of ◽

Dmd Gene ◽

Treatment Expectation ◽

Dependent Probe ◽

Short Tandem

Abstract Objective DMD/BMD prenatal diagnosis for 931 foetuses. Background DMD is the most common fatal X-linked recessive muscular disease. There is no effective clinical treatment method at present. Accurate gene diagnosis and prenatal diagnosis technology are important ways for early detection, early prevention and early treatment. Methods A total of 931 prenatal diagnoses were performed for pregnant women with a definite family history of DMD or a history of DMD childbirth between 2005 and 2019. This report may be considered the largest DMD prenatal diagnosis report in a single centre worldwide. Multiple ligation-dependent probe amplification (MLPA) and next-generation sequencing were used in combination. Techniques and short tandem repeat (STR) linkage analysis were used to determine the location of the DMD gene mutation in the pregnant woman and then to detect the DMD gene in the foetuses. Results There were 872 families in our study. Among all 931 foetuses, 20.73% (193/931) were males expected to develop DMD and 16.33% (152/931) were female carriers. In addition, gonadal mosaicism was observed in 5 mothers, and gene recombination was identified in three foetuses. The results of the prenatal diagnosis were consistent with the results of the CPK analysis, and the results of the prenatal diagnosis were 100% accurate. Conclusions MLPA and Sanger sequencing, when combined with STR linkage analyses, can provide an accurate and rapid prenatal diagnosis. Due to the high de novo rate, prenatal diagnosis and genetic counselling should be given great attention.

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Molecular Diagnosis and Prenatal Counseling of a Chinese Family with Spondyloepiphyseal Dysplasia congenital

10.21203/rs.3.rs-497606/v1 ◽

2021 ◽

Author(s):

Lihong Fan ◽

Yuqing Xu ◽

Guosong Shen ◽

Xueping Shen ◽

Kefeng Tang ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Gene Mutation ◽

Sanger Sequencing ◽

Chromosome Analysis ◽

Type Ii Collagen ◽

Chinese Family ◽

Prenatal Counseling ◽

Targeted Next Generation Sequencing ◽

Spondyloepiphyseal Dysplasia ◽

Next Generation Sequencing Ngs

Abstract Aim: To identify the gene mutation and complete prenatal counseling in a Chinese family with spondyloepiphyseal dysplasia congenital (SEDC). Materials and Methods: A Chinese family with SEDC was enrolled. Their detailed clinical features, skeletal radiographic features, and laboratory results were obtained. The peripheral blood samples of the family members were used for the targeted next-generation sequencing (NGS), and Sanger sequencing confirmation. Bioinformatics analysis and genotype-phenotype correlation analysis were used to identify the gene mutation. Amniocentesis, fetal chromosome analysis and Sanger sequencing were completed for prenatal diagnosis. Results: A missense mutation c.3392G>T (p. Gly1131Val) of COL2A1 was found in the proband and the fetus. The mutation was confirmed to be likely pathogenic and would damage the structure of stable triple-helical type II collagen. Conclusion: A novel pathogenic c.3392G>T (p. Gly1131Val) mutation in COL2A1 leading to SEDC was identified, which expanded the genotypic spectrum and phenotypic spectrum of SEDC. In addition, we wish to emphasize that prenatal diagnosis and genetic counseling should be carried out in a family with SEDC for better procreative management.

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Prenatal diagnosis of Duchenne muscular dystrophy and cytogenetic analysis in 303 Chinese families

10.21203/rs.3.rs-16316/v1 ◽

2020 ◽

Author(s):

Mengmeng Li ◽

Fengxia Yao ◽

Na Hao ◽

Weimin Zhang ◽

Jing Zhou ◽

...

Keyword(s):

Retrospective Study ◽

Prenatal Diagnosis ◽

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Pregnant Women ◽

Gene Mutation ◽

Trisomy 21 ◽

Karyotype Analysis ◽

Chinese Families ◽

Dmd Gene

Abstract Background: Duchenne muscular dystrophy (DMD) has showed a wide spectrum of mutations in the dystrophin gene including exon deletions, duplications and small mutations. This retrospective study was to supply information of the DMD mutational spectrum in 303 Chinese families and further offer 5-year clinical experience of DMD genetic counselling and prenatal diagnosis.Methods: In this retrospective study, 305 pregnancies in 303 pregnant women who has a birth history of DMD patients underwent prenatal diagnosis using multiplex ligation-dependent probe amplification (MLPA) followed by Sanger sequencing between 2014 and 2018. Karyotype analysis was performed to exclude fetal abnormal karyotype.Results: The detection rate of DMD gene mutation in 303 probands was 97.7% with 7 families having a negative genetic diagnosis. The mutational spectrum comprised of large arrangements in 288/303 (95.0%) and small mutations in 8/303 (2.6%). 204 pregnant women did carrier testing among whom, 108 mothers had the same mutation as family proband. Of the 305 pregnancies underwent prenatal diagnosis, 55 of 173 male fetuses were affected. We also performed karyotype analysis and found 3 abnormal karyotypes of trisomy 21. We even found a fetus with DMD gene mutation and trisomy 21 in a same fetus by further analysis.Conclusions: The distribution and mutation profile of 303 probands and 305 fetuses were demonstrated. Given the large samples provided in this study, the information is essential for genetic counselling and prenatal diagnosis in DMD families in China.

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