scholarly journals Prenatal diagnosis of Duchenne muscular dystrophy revealed a novel mosaic mutation in Dystrophin gene: a case report

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yan Wang ◽  
Yuhan Chen ◽  
San Mei Wang ◽  
Xin Liu ◽  
Ya Nan Gu ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Sanger Sequencing ◽  
De Novo ◽  
Novel Mutation ◽  
Neuromuscular Disorders ◽  
Genetic Diagnosis ◽  
Dystrophin Gene ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Dmd Gene

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.

scholarly journals Genetic, Prenatal, and Preimplantation Genetic Diagnosis of Glutaric Aciduria Type I

2021 ◽  
Vol 3 (1) ◽  
pp. 397-404
Author(s):  
He B ◽  
Wang L ◽  
Wu Q ◽  
Song C ◽  
Li W ◽  
...  
Keyword(s):  
Sanger Sequencing ◽  
Treatment Guidelines ◽  
Genetic Diagnosis ◽  
Monogenic Disease ◽  
Compound Heterozygous Mutation ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Type I ◽  
Preimplantation Genetic Testing

Purpose: Glutaric Acid Type I (GA-I) is an inherited metabolic disorder. Although the treatment guidelines for GA-I were established a decade ago, they cannot block the vertical heredity. We aim to apply genetic methods to block the inheritance of GA-I and verifies the efficiency of Next-Generation Sequencing (NGS)-based Preimplantation Genetic Testing for Monogenic disease (PGT-M) of GA-I.Materials and methods: A non-consanguineous Chinese family was diagnosed with GA-I by Sanger sequencing. PGT-M and prenatal diagnosis (PND) were performed for the carrier. 5 blastocysts were used for the trophectoderm biopsy. After Whole-Genome Amplification (WGA), the WGA products were used for Sanger sequencing, NGS-based PGT-M and PGT-A. Sanger sequencing-based PND was performed in second trimester to confirm the results of PGT-M.Results: A compound heterozygous mutation was diagnosed in the GCDH gene with co-segregation. One is [c.533G>A (p.G178E)] and another is [c.914C>T (p.S305L)]. 2 blastocysts were diagnosed as normal and one of them was transferred into the mother’s uterus. Finally, a healthy female was born 39 weeks after transplantation.Conclusion: Our study successfully applied NGS-based PGT-M to avoid GA-I and highlights the efficiency of genetic diagnoses. It has significant implications on genetic counseling and genetic diagnosis for GA-I.

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

Medicine ◽  
2017 ◽  
Vol 96 (50) ◽  
pp. e8814 ◽  
Author(s):  
Tao Li ◽  
Zhao-jing Zhang ◽  
Xin Ma ◽  
Xue Lv ◽  
Hai Xiao ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Gene Mutation ◽  
De Novo ◽  
Chinese Family ◽  
Dmd Gene

scholarly journals Identification of a Heterozygous Mutation in the TGFBI Gene in a Hui-Chinese Family with Corneal Dystrophy

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Qin Xiang ◽  
Lamei Yuan ◽  
Yanna Cao ◽  
Hongbo Xu ◽  
Yunfeiyang Li ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Transforming Growth Factor ◽  
Corneal Dystrophy ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Type I ◽  
Whole Exome ◽  
The Family

Background/Aims. Corneal dystrophies (CDs) belong to a group of hereditary heterogeneous corneal diseases which result in visual impairment due to the progressive accumulation of deposits in different corneal layers. So far, mutations in several genes have been responsible for various CDs. The purpose of this study is to identify gene mutations in a three-generation Hui-Chinese family associated with granular corneal dystrophy type I (GCD1). Methods. A three-generation Hui-Chinese pedigree with GCD1 was recruited for this study. Slit-lamp biomicroscopy, optical coherence tomography, and confocal microscopy were performed to determine the clinical features of available members. Whole exome sequencing was performed on two patients to screen for potential disease-causing variants in the family. Sanger sequencing was used to test the variant in the family members. Results. Clinical examinations demonstrated bilaterally abundant multiple grayish-white opacities in the basal epithelial and superficial stroma layers of corneas of the two patients. Whole exome sequencing revealed that a heterozygous missense mutation (c.1663C > T, p.Arg555Trp) in the transforming growth factor beta-induced gene (TGFBI) was shared by the two patients, and it cosegregated with this disease in the family confirmed by Sanger sequencing. Conclusions. The results suggested that the heterozygous TGFBI c.1663C > T (p.Arg555Trp) mutation was responsible for GCD1 in the Hui-Chinese family, which should be of great help in genetic counseling for this family.

New and Inherited STAT1 Mutations in a Chinese Family with Chronic Mucocutaneous Candidiasis: A Case Report

2020 ◽  
Author(s):  
Xiaoheng XU ◽  
Wenxia MENG ◽  
Lu FENG ◽  
Wei GUO
Keyword(s):  
Human Gene ◽  
Genetic Diagnosis ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Chronic Mucocutaneous Candidiasis ◽  
Dna Binding Domain ◽  
Oral Medicine ◽  
Mucocutaneous Candidiasis ◽  
Mutation Database ◽  
First Time

A mild clinical Chronic Mucocutaneous Candidiasis (CMC) phenotype with STAT1 transcription factor mutation has been identified in a Chinese family. It is a rare variant in STAT1 (NM_0073315.3c.1175T>C Met392Thr). Specifically, it is a heterozygous mutation. To date, the pathogenicity of this variant in STAT1 (NM_0073315.3c.1175T>C Met392Thr) for CMC has not been reported in the Human Gene Mutation Database. Thus, this is the first report about STAT1 mutation found in CMC patients from Chinese ethnic group. This study also shows the mutation on the DNA-binding domain of STAT1 for the first time. The findings will broaden the spectrum of STAT1 mutations and facilitate genetic diagnosis by the oral medicine specialists.

scholarly journals Novel de novo heterozygous mutation on SYNGAP1 from the Indian population

2020 ◽  
Author(s):  
Vijaya Verma ◽  
Amit Mandora ◽  
Abhijeet Botre ◽  
James Premdoss Clement
Keyword(s):  
Exome Sequencing ◽  
De Novo ◽  
Novel Mutation ◽  
Autism Spectrum ◽  
Current Treatment ◽  
Developmental Trajectory ◽  
Global Developmental Delay ◽  
Heterozygous Mutation ◽  
Specific Gene ◽  
De Novo Mutations

Abstract Background : Exome sequencing is a prominent tool to identify novel and deleterious mutations which could be nonsense, frameshift, and canonical splice-site mutations in a specific gene. De novo mutations in SYNGAP1 , which codes for synaptic RAS-GTPase activating the protein, causes Intellectual disability (ID) and Autism Spectrum Disorder (ASD). SYNGAP1 related ASD/ID is one of the rare diseases that is detrimental to the normal neuronal developmental and disrupts the global development of a child. Results: We report a case of a child of 2-year old with global developmental delay, microcephaly subtle dysmorphism, absence seizures, disrupted sleep, delay in learning a language, and eating problems. Upon further validation, the child has a few traits of ASD. Here, based on focused exome sequencing, we report a de novo heterozygous mutation in SYNGAP1 exon 11 with c. 1861 C>T (p.arg612ter). Currently, the child is on atorvastatin and has shown considerable improvement in global behaviour and cognitive development. The long-term follow up of the child’s development would contribute to the already existing knowledge of the developmental trajectory in individuals with SYNGAP1 heterozygous mutation. Conclusion: In this report, we discuss the finding of a novel mutation in one of the genes, SYNGAP1 , implicated in ASD/ID. In addition, we discuss the current treatment prescribed to the patient and the progress of global developmental of the child.

Duchenne Muscular Dystrophy and Early Onset Hypertrophic Cardiomyopathy associated with Mutations in Dystrophin and Hypertrophic Cardiomyopathy-Associated Genes

2020 ◽  
Author(s):  
Liam Aspit ◽  
Noga Arwas ◽  
Aviva Levitas ◽  
Hanna Krymko ◽  
Yoram Etzion ◽  
...  
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Hypertrophic Cardiomyopathy ◽  
Muscular Dystrophy ◽  
Early Onset ◽  
De Novo ◽  
Genetic Diagnosis ◽  
Dystrophin Gene ◽  
Whole Exome ◽  
Rare Phenotype ◽  
Muscular Damage

AbstractDuchenne muscular dystrophy (DMD) is a progressive muscular damage disorder caused by mutations in dystrophin gene. Cardiomyopathy may first be evident after 10 years of age and increases in incidence with age. We present a boy diagnosed at 18 months with a rare phenotype of DMD in association with early-onset hypertrophic cardiomyopathy (HCM). The cause of DMD is a deletion of exons 51–54 of dystrophin gene. The cause of HCM was verified by whole exome sequencing. Novel missense variations in two genes: MAP2K5 inherited from the mother and ACTN2 inherited from the father, or de novo. The combination of MAP2K5, ACTN2, and dystrophin mutations, could be causing the HCM in our patient. This is the second patient diagnosed, at relatively young age, with DMD and HCM, with novel variations in genes known to cause HCM. This study demonstrates the need for genetic diagnosis to elucidate the underlying pathology of HCM.

scholarly journals Genetic analysis of 62 Chinese families with Duchenne muscular dystrophy and strategies of prenatal diagnosis in a single center

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Jingjing Zhang ◽  
Dingyuan Ma ◽  
Gang Liu ◽  
Yuguo Wang ◽  
An Liu ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
De Novo ◽  
Clinical Symptoms ◽  
Perinatal Care ◽  
Genetic Diagnosis ◽  
Point Mutations ◽  
Inherited Disease ◽  
Positive Results

Abstract Background Duchenne muscular dystrophy (DMD) is a severe X-linked recessive neuromuscular disorder. Patients with DMD usually have severe and fatal symptoms, including progressive irreversible muscle weakness and atrophy complicated with gastrocnemius muscle pseudohypertrophy. DMD is caused by mutations in the dystrophin-encoding DMD gene, including large rearrangements and point mutations. This retrospective study was aimed at supplying information on our 4-year clinical experience of DMD genetic and prenatal diagnosis at the Department of Prenatal Diagnosis in Women’s Hospital of Nanjing Medical University. Methods Multiplex ligation-dependent probe amplification (MLPA) was used to detect the exon deletions or duplications. And Ion AmpliSeq™ panel for inherited disease was used as the next-generation sequencing (NGS) method to identify the point mutations in exons of DMD gene, but the introns were not sequenced. Results In this study, the large deletions and duplications of DMD gene were detected in 32 (51.6%) of the 62 families, while point mutations were detected in 20 families (32.3%). The remaining 10 families with a negative genetic diagnosis need to be reevaluated for clinical symptoms or be detected by other molecular methods. Notably, six novel mutations were identified, including c.412A > T(p.Lys138*), c.2962delT(p.Ser988Leufs*16), c.6850dupA (p.Ser2284Lysfs*7), c.5139dupA (p.Glu 1714Argfs*5), c.6201_6203delGCCins CCCA(p.Val2069Cysfs*14) and c.10705A > T (p.Lys3569*). In 52 families with positive results, 45 mothers (86.5%) showed positive results during carrier testing and de novo mutations arose in 7 probands. The prenatal diagnosis was offered to 34 fetuses whether the pregnant mother was a carrier or not. As a result, eight male fetuses were affected, three female fetuses were carriers, and the remaining fetuses had no pathogenic mutation. Conclusions This study reported that MLPA and NGS could be used for screening the DMD gene mutations. Furthermore, the stepwise procedure of prenatal diagnosis of DMD gene was shown in our study, which is important for assessing the mutation type of fetuses and providing perinatal care in DMD high-risk families.

scholarly journals A Novel Nonsense Mutation ofPOU4F3Gene Causes Autosomal Dominant Hearing Loss

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Chi Zhang ◽  
Mingming Wang ◽  
Yun Xiao ◽  
Fengguo Zhang ◽  
Yicui Zhou ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Nonsense Mutation ◽  
Autosomal Dominant ◽  
Late Onset ◽  
Stop Codon ◽  
Novel Mutation ◽  
Genetic Diagnosis ◽  
Chinese Family ◽  
Nonsyndromic Hearing Loss ◽  
Truncated Protein

POU4F3gene encodes a transcription factor which plays an essential role in the maturation and maintenance of hair cells in cochlea and vestibular system. Several mutations ofPOU4F3have been reported to cause autosomal dominant nonsyndromic hearing loss in recent years. In this study, we describe a pathogenic nonsense mutation located inPOU4F3in a four-generation Chinese family. Target region capture sequencing was performed to search for the candidate mutations from 81 genes related to nonsyndromic hearing loss in this family. A novel nonsense mutation ofPOU4F3, c.337C>T (p.Gln113⁎), was identified in a Chinese family characterized by late-onset progressive nonsyndromic hearing loss. The novel mutation cosegregated with hearing loss in this family and was absent in 200 ethnicity-matched controls. The mutation led to a stop codon and thus a truncated protein with no functional domains remained. Transient transfection and immunofluorescence assay revealed that the subcellular localization of the truncated protein differed markedly from normal protein, which could be the underlying reason for complete loss of its normal function. Here, we report the first nonsense mutation ofPOU4F3associated with progressive hearing loss and explored the possible underlying mechanism. Routine examination ofPOU4F3is necessary for the genetic diagnosis of hereditary hearing loss in the future.

A novel mutation in the glutamate dehydrogenase (GLUD1) of a patient with congenital hyperinsulinism-hyperammonemia (HI/HA)

2016 ◽  
Vol 29 (3) ◽  
Author(s):  
Chen Fang ◽  
Xin Ding ◽  
Yun Huang ◽  
Jian Huang ◽  
Pengjun Zhao ◽  
...  
Keyword(s):  
Birth Weight ◽  
Missense Mutation ◽  
Glutamate Dehydrogenase ◽  
De Novo ◽  
Novel Mutation ◽  
Genetic Diagnosis ◽  
Congenital Hyperinsulinism ◽  
Normal Birth Weight ◽  
Normal Birth

AbstractHyperinsulinism-hyperammonemia (HI/HA) syndrome, often characterized by recurrent symptomatic hypoglycemia and persistent hyperammonemia, is the second most frequent cause of the congenital hyperinsulinism (CHI). Here, we reported a patient with normal birth weight, repeated seizures, untreatable hypoglycemia, and persistent, mild hyperammonemia. The genetic diagnosis revealed that the patient carried a heterozygous, de novo missense mutation (N410I, c.1401A>T) in the glutamate dehydrogenase 1 gene (

A Novel IRF6 Frameshift Mutation in a Large Chinese Pedigree With Van der Woude syndrome

2021 ◽  
pp. 105566562110109
Author(s):  
Qi Peng ◽  
Wenyan Qin ◽  
Siping Li ◽  
Meihua Huang ◽  
Chunbao Rao ◽  
...  
Keyword(s):  
Stop Codon ◽  
Novel Mutation ◽  
Genetic Diagnosis ◽  
Premature Stop Codon ◽  
Chinese Family ◽  
The Novel ◽  
Protein Alignment ◽  
Van Der Woude Syndrome ◽  
Psychological Burden ◽  
Irf6 Gene

Aims: Van der Woude syndrome (VWS) is one of the most common craniofacial anomalies, causing significant functional and psychological burden to the patients. This study aimed to identify the genetic cause of VWS in a Chinese family. Methods: Whole genome sequencing (WGS) was performed to screen for pathogenic mutations. Various Bioinformatics tools were used to assess the pathogenicity of the variants. Cosegregation analysis of the candidate variant was carried out. Interpretation of variants was performed according to the American College of Medical Genetics and Genomics guidelines. Results: A novel frameshift duplication c.373_374dupAA (p.Asn125Lys fs*43) was identified in exon 4 of the interferon regulatory factor 6 (IRF6) gene in all 3 affected members, which were not found in unaffected family members. The novel mutation leads to a frameshift and a premature stop codon which caused putative truncated protein. Protein alignment indicated high evolutionary conservation of the p.N125 residue, and this mutation was predicted by online tools to be damaging and deleterious. Conclusions: This study demonstrates that the novel mutation c.373_374dupAA (p.Asn125Lysfs*43) in the IRF6 gene corresponds to the VWS in this family. The discovery of this pathogenic variant enriches the genotypic spectrum of IRF6 gene and contributes to genetic diagnosis and counseling of families with VWS.

Sign in / Sign up

Export Citation Format

Share Document