scholarly journals Compound heterozygous variants of the FBXO7 gene resulting in infantile‐onset Parkinsonian‐pyramidal syndrome in siblings of a Chinese family

2020 ◽  
Vol 34 (8) ◽  
Author(s):  
Xiaohua Jin ◽  
Lisha An ◽  
Shengju Hao ◽  
Qian Liu ◽  
Qinhua Zhang ◽  
...  
Keyword(s):  
Chinese Family ◽  
Compound Heterozygous ◽  
Pyramidal Syndrome ◽  
Compound Heterozygous Variants

scholarly journals Novel compound heterozygous EYS variants may be associated with arRP in a large Chinese pedigree

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Chunli Wei ◽  
Ting Xiao ◽  
Jingliang Cheng ◽  
Jiewen Fu ◽  
Qi Zhou ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Gene Mutations ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Missense Mutations ◽  
The Novel ◽  
Pathogenic Variants ◽  
Pathogenic Genes ◽  
Compound Heterozygous Variants ◽  
Normal Controls

Abstract As a genetically heterogeneous ocular dystrophy, gene mutations with autosomal recessive retinitis pigmentosa (arRP) in patients have not been well described. We aimed to detect the disease-causing genes and variants in a Chinese arRP family. In the present study, a large Chinese pedigree consisting of 31 members including a proband and another two patients was recruited; clinical examinations were conducted; next-generation sequencing using a gene panel was used for identifying pathogenic genes, and Sanger sequencing was performed for verification of mutations. Novel compound heterozygous variants c.G2504A (p.C835Y) and c.G6557A (p.G2186E) for the EYS gene were identified, which co-segregated with the clinical RP phenotypes. Sequencing of 100 ethnically matched normal controls didn’t found these mutations in EYS. Therefore, our study identified pathogenic variants in EYS that may cause arRP in this Chinese family. This is the first study to reveal the novel mutation in the EYS gene (c.G2504A, p.C835Y), extending its mutation spectrum. Thus, the EYS c.G2504A (p.C835Y) and c.G6557A (p.G2186E) variants may be the disease-causing missense mutations for RP in this large arRP family. These findings should be helpful for molecular diagnosis, genetic counseling and clinical management of arRP disease.

scholarly journals Novel MFSD8 Variants in a Chinese Family with Nonsyndromic Macular Dystrophy

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Qin Xiang ◽  
Yanna Cao ◽  
Hongbo Xu ◽  
Zhijian Yang ◽  
Liang Tang ◽  
...  
Keyword(s):  
Family Members ◽  
Major Facilitator Superfamily ◽  
Chinese Family ◽  
Macular Dystrophy ◽  
Compound Heterozygous ◽  
The Novel ◽  
Pathogenic Variants ◽  
Compound Heterozygous Variants ◽  
Major Facilitator ◽  
Mfsd8 Gene

Purpose. To identify the molecular etiology of a Chinese family with nonsyndromic macular dystrophy. Methods. Ophthalmic examinations were performed, and genomic DNA was extracted from available family members. Whole exome sequencing of two members (the proband and her unaffected mother) and Sanger sequencing in available family members were performed to screen potential pathogenic variants. Results. Novel compound heterozygous variants, c.1066C>T (p.Pro356Ser) and c.1102+2T>C, in the major facilitator superfamily domain containing 8 gene (MFSD8) were suspected to be involved in this family’s macular dystrophy phenotype. The novel c.1066C>T variant in the MFSD8 gene probably resulted in substitution of serine for proline at the 356th residue and was predicted to be “uncertain significance” through in silico analyses. The novel c.1102+2T>C variant in the MFSD8 gene was likely to affect the splicing form and predicted to be “pathogenic.” Conclusion. The novel compound heterozygous variants, c.1066C>T (p.Pro356Ser) and c.1102+2T>C, in the MFSD8 gene are likely responsible for the isolated macular dystrophy phenotype in this family. This study enlarged the MFSD8 gene mutant spectrum and might provide more accurate genetic counseling for this family.

scholarly journals DNAH11 compound heterozygous variants cause heterotaxy and congenital heart disease

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252786
Author(s):  
Hong Xia ◽  
Xiangjun Huang ◽  
Sheng Deng ◽  
Hongbo Xu ◽  
Yan Yang ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Exome Sequencing ◽  
Sanger Sequencing ◽  
Congenital Heart ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Internal Organs ◽  
Pathogenic Variants ◽  
Compound Heterozygous Variants

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.

Novel compound heterozygous variants in the STIL gene identified in a Chinese family with presentation of foetal microcephaly

2020 ◽  
Vol 63 (12) ◽  
pp. 104091
Author(s):  
Chen Cheng ◽  
Ying Yang ◽  
Xia Zhu ◽  
Xudong Yu ◽  
Tongda Zhang ◽  
...  
Keyword(s):  
Chinese Family ◽  
Compound Heterozygous ◽  
Compound Heterozygous Variants

scholarly journals Type I interferonopathies with novel compound heterozygous TREX1 mutations in two siblings with different symptoms responded to tofacitinib

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Shiyu Zhang ◽  
Jiaxing Song ◽  
Yuyan Yang ◽  
Huilei Miao ◽  
Lu Yang ◽  
...  
Keyword(s):  
Mutation Screening ◽  
Missense Variant ◽  
Skin Lesions ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Therapeutic Effects ◽  
Type I ◽  
Her Family ◽  
Compound Heterozygous Variants ◽  
Type I Interferonopathies

Abstract Background Type I interferonopathies are a group of rare autoimmune diseases characterised by excessive activation of type I interferon that leads to disturbances in immune function. Three prime repair exonuclease 1 (TREX1) is an important exonuclease and plays an important role in DNA damage repair. TREX1 mutations are associated with many type I interferonopathies. Studies have been published on the effectiveness of tofacitinib in the treatment of type I interferonopathies. The aim of this study is to identify the pathogenic variation in a Chinese family with type I interferonopathies and to observe the therapeutic effects of tofacitinib. Methods A Chinese family with two members with type I interferonopathies was investigated. Whole exome sequencing and Sanger sequencing were applied for mutation screening using peripheral blood DNA of the patient and her family members. Sequencing results were analysed using bioinformatics software tools including VarCards and PolyPhen-2. Close clinical follow-up and observation were used to record changes in the disease before and after treatment with tofacitinib. Results Compound heterozygous variants of TREX1 were observed in the patient’s genome. One was a missense variant (NM_016381; c.C227T; p.Ala76Val) from the patient’s father, and the other was a frameshift variant (NM_016381; c.458dupA; p.Gln153Glnfs*3) from the patient’s mother. One of the proband’s elder brothers with similar skin lesions also carried these two variants. This brother of the proband had more serious cutaneous involvement with the comorbidity of cerebral palsy. These TREX1 variants have not been reported in previous studies and are predicted to be highly pathogenic. The proband was given tofacitinib that led to a marked improvement. Conclusions We identified two novel complex heterozygous variants in the TREX1 gene, which may underlie the molecular pathogenesis of the type I interferonopathies observed in members of this family. Tofacitinib could be an alternative treatment for this disease.

scholarly journals Novel Compound Heterozygous Variants of DYNC2H1 Causing The Short Rib-Polydactyly Syndrome, Type III With Situs Inversus Totalis in a Fetus

2021 ◽  
Author(s):  
Chen Cheng ◽  
Sheng Zhao ◽  
Qian Feng ◽  
Xinlin Chen
Keyword(s):  
Situs Inversus ◽  
Clinical Signs ◽  
Autosomal Recessive Disorder ◽  
Situs Inversus Totalis ◽  
Mirror Image ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Or Gene ◽  
Short Rib Polydactyly Syndrome ◽  
Compound Heterozygous Variants

Abstract Background Short-rib thoracic dysplasia 3 with or without polydactyly (SRTD3) is an autosomal recessive disorder. SRTD3 presents clinically with the narrow thorax, short ribs, shortened tubular bones, and acetabular roof abnormalities. Clinical signs of SRTD3 vary among individuals. Mutations of DYNC2H1 were reported to cause SRTD3. Methods We performed a detailed clinical prenatal sonographic characterization of the fetus with SRTD3. Whole-exome sequencing was used to identify causative variants in the trio family. The identified variants were validated by Sanger sequencing and mass spectrometry in the families. Multiple computational tools were used to predict the harmfulness of the two variants. Results We presented with the prenatal sonographic image of the fetus with SRTD3, including abnormal rib curvature, narrow thorax, bilateral hypoplastic lungs, bilateral polydactyly, syndactyly and fetal visceral situs inversus with mirror-image dextrocardia. We revealed novel compound variants of DYNC2H1 (NM_001080463.1: c.11504T > G (p.Ile3835Arg) and c.2106 + 3A > T). Various statistical methods predicted that the variants would cause harmful effects on genes or gene products. Conclusion It is the first time that fetal SRTD3 with situs inversus totalis in a Chinese family. Our study not only revealed two novel compound heterozygous Dynein Cytoplasmic 2 Heavy Chain 1 (DYNC2H1) variants, expanding the genetic spectrum of SRTD3 but also raising the new phenotype. Our study helps add experience to further our expertise in prenatal counseling for SRTD3.

scholarly journals Novel Compound Heterozygous PRKN Variants in a Han-Chinese Family with Early-Onset Parkinson’s Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Kuan Fan ◽  
Pengzhi Hu ◽  
Chengyuan Song ◽  
Xiong Deng ◽  
Jie Wen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Onset ◽  
Genetic Factors ◽  
Genetic Diagnosis ◽  
Han Chinese ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Compound Heterozygous Variants ◽  
Early Onset Parkinson’S Disease

Genetic factors are thought to play an important role in the pathogenesis of Parkinson’s disease (PD), particularly early-onset PD. The PRKN gene is the primary disease-causing gene for early-onset PD. The details of its functions remain unclear. This study identified novel compound heterozygous variants (p.T240K and p.L272R) of the PRKN gene in a Han-Chinese family with early-onset PD. This finding is helpful in the genetic diagnosis of PD and also the functional research of the PRKN gene.

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