scholarly journals IFNAR1 gene mutation may contribute to developmental stuttering in the Chinese population

Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Yimin Sun ◽  
Yong Gao ◽  
Yuxi Zhou ◽  
Yulong Zhou ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Chinese Population ◽  
Sanger Sequencing ◽  
Chinese Family ◽  
Type I ◽  
Chinese Families ◽  
Whole Exome ◽  
Persistent Developmental Stuttering ◽  
Sporadic Cases ◽  
Developmental Stuttering

Abstract Background Developmental stuttering is the most common form of stuttering without apparent neurogenic or psychogenic impairment. Recently, whole-exome sequencing (WES) has been suggested to be a promising approach to study Mendelian disorders. Methods Here, we describe an application of WES to identify a gene potentially responsible for persistent developmental stuttering (PDS) by sequencing DNA samples from 10 independent PDS families and 11 sporadic cases. Sanger sequencing was performed for verification with samples obtained from 73 additional patients with sporadic cases. Results We first searched for cosegregating variants/candidate genes in a Chinese family (Family 0) by sequencing DNA obtained from 3 affected members and 3 controls. Next, we sequenced DNA samples obtained from 9 additional Chinese families (Families 1-9) with stuttering to verify the identified candidate genes. Intriguingly, we found that two missense variants (Leu552Pro and Lys428Gln) of interferon-alpha/beta receptor 1 (IFNAR1) cosegregated with stuttering in three independent families (Families 0, 5 and 9). Moreover, we found two additional mutations (Gly301Glu and Pro335del) in the IFNAR1 gene in 4 patients with sporadic cases by using WES or Sanger sequencing. Further receptor mutagenesis and cell signaling studies revealed that these IFNAR1 variants may impair the activity of type I IFN signaling. Conclusion Our data indicate that IFNAR1 might be a potential pathogenic gene of PDS in the Chinese population.

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.

Mutation of COL2A1 in a Chinese Family with Presentations of Legg-Calvé-Perthes Disease

2020 ◽  
Author(s):  
denglu yan ◽  
zhaojie Wang ◽  
Zhi Zhang
Keyword(s):  
Femoral Head ◽  
Sanger Sequencing ◽  
Structural Changes ◽  
Genetic Factors ◽  
Mutation Detection ◽  
Perthes Disease ◽  
Chinese Family ◽  
Col2a1 Gene ◽  
Whole Exome ◽  
Missense Substitution

Abstract Background: The aim of this study was to identify genetic factors and chromosomal regions contributing to osteonecrosis of the femoral head (ONFH) in a Chinese family with presentations of Legg-Calvé-Perthes Disease (LCDP). Methods: In this study, we performed whole exon sequencing of a Chinese family with LCPD for mutation detection. Ten members had ONFH in twenty-seven family members in four generations family, 5 unaffected members of the studied family and 5 normal peoples as control were underwent whole exome sequencing for mutation detection. Structural modeling test was applied to analyze the potential structural changes caused by the missense substitution. Results: In this Chinese family affected by LCPD, the mutation (c.3508 G>A, p. Gly1170Ser) in exon 50 of COL2A1 in the Gly–X–Y domain was present in 10 patients but absent in 5 unaffected members of the studied family and in 5 control chromosomes from unaffected individuals of matched geographical ancestry. The COL2A1 gene mutation was further validated by Sanger sequencing, confirmed that were heterozygous for the mutation. Then, we identified the p.Gly1170Ser mutation in exon 50 of COL2A1 in a Chinese family with LCPD. Conclusions: This study maps the mutation of mutation (c.3508 G>A, p. Gly1170Ser) in exon 50 of COL2A1 in the Gly–X–Y domain in a Chinese family of LCPD, which causes osteonecrosis of femoral head.

Whole Exome Sequencing of Six Chinese Families With Hereditary Non-Syndromic Hearing Loss: A Genetic Etiology Study

2020 ◽  
Author(s):  
Pengfei Liang ◽  
Fengping Chen ◽  
Shujuan Wang ◽  
Qiong Li ◽  
Wei Li ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Large Scale ◽  
Autosomal Recessive ◽  
Autosomal Recessive Inheritance ◽  
Chinese Families ◽  
Whole Exome ◽  
Syndromic Hearing Loss

Abstract Background: Hereditary non-syndromic hearing loss (NSHL) has a high genetic heterogeneity with >152 genes identified as associated molecular causes. The present study aimed to detect the possible damaging variants of the deaf probands from six unrelated Chinese families.Methods: After excluding the mutations in the most common genes, GJB2 and SLC26A4, 12 probands with prelingual deafness and autosomal recessive inheritance were evaluated by whole-exome sequencing (WES). All the candidate variants were verified by Sanger sequencing in all patients and their parents.Results: Biallelic mutations were identified in all deaf patients. Among these six families, 10 potentially causative mutations, including 3 reported and 7 novel mutations, in 3 different deafness-associated autosomal recessive (DFNB) genes (MYO15A, COL11A2, and CDH23) were identified. The mutations in MYO15A were frequent with 7/10 candidate variants. Sanger sequencing confirmed that these mutations segregated with the hearing loss of each family.Conclusions: Next-generation sequencing (NGS) approach becomes more cost-effective and efficient when analyzing large-scale genes compared to the conventional polymerase chain reaction-based Sanger sequencing, which is often used to screen common deafness-related genes. The current findings further extend the mutation spectrum of hearing loss in the Chinese population, which has a positive significance for genetic counseling.

scholarly journals Case report: two novel VPS13B mutations in a Chinese family with Cohen syndrome and hyperlinear palms

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Sha Zhao ◽  
Zhenqing Luo ◽  
Zhenghui Xiao ◽  
Liping Li ◽  
Rui Zhao ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Chinese Population ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Case Presentation ◽  
Cohen Syndrome ◽  
The Family ◽  
Sporadic Cases

Abstract Background Cohen syndrome (CS) is an uncommon developmental disease with evident clinical heterogeneity. VPS13B is the only gene responsible for CS. Only few sporadic cases of CS have been reported in China. Case presentation A Chinese family with two offspring–patients affected by developmental delay and intellectual disability was investigated in this study. Exome sequencing was performed, and compound heterozygous mutations in VPS13B were segregated for family members with autosomal recessive disorder. Splicing mutation c.3666 + 1G > T (exon 24) and nonsense mutation c. 9844 A > T:p.K3282X (exon 54) were novel. We revisited the family and learned that both patients are affected by microcephaly, developmental delay, neutropenia, and myopia and have a friendly disposition, all of which are consistent with CS phenotypes. We also found that both patients have hyperlinear palms, which their parents do not have. VPS13B mutations reported among the Chinese population were reviewed accordingly. Conclusions This study presents two novel VPS13B mutations in CS. The identification of hyperlinear palms in a family affected by CS expands the phenotype spectrum of CS.

scholarly journals A Novel BBS9 Mutation Identified via Whole-Exome Sequencing in a Chinese Family with Bardet-Biedl Syndrome

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Yue Zhang ◽  
Manhong Xu ◽  
Minglian Zhang ◽  
Guoxing Yang ◽  
Xiaorong Li
Keyword(s):  
Mental Retardation ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Chinese Family ◽  
Cone Dystrophy ◽  
Bardet Biedl Syndrome ◽  
Homozygous Variant ◽  
Whole Exome

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized by polydactyly, obesity, rod-cone dystrophy, and mental retardation. Twenty-one genes have been identified as causing BBS. This study collected a BBS pedigree from two patients and performed whole-exome sequencing on one patient. We identified a novel homozygous variant c.1114C>T (p.Q372X) in the BBS9 of the two siblings. This variant was confirmed and completely cosegregated with the disease of this family by Sanger sequencing. We report a novel homozygous variant c.1114C>T in the BBS9 gene in a Chinese family.

scholarly journals A Novel Missense Variant of TP63 Heterozygously Present in Split-Hand/Foot Malformation

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Hao Geng ◽  
Dongdong Tang ◽  
Chuan Xu ◽  
Xiaojin He ◽  
Zhiguo Zhang
Keyword(s):  
Blood Sample ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Peripheral Blood ◽  
Sanger Sequencing ◽  
Missense Variant ◽  
Chinese Family ◽  
Peripheral Blood Sample ◽  
Whole Exome ◽  
Novel Variant

Background. Split-hand/foot malformation (SHFM) is a severe congenital disability mainly characterized by the absence or hypoplasia of the central ray of the hand/foot. To date, several candidate genes associated with SHFM have been identified, including TP63, DLX5, DLX6, FGFR1, and WNT10B. Herein, we report a novel variant of TP63 heterozygously present in affected members of a family with SHFM. Methods. This study investigated a Chinese family, in which the proband and his son suffered from SHFM. The peripheral blood sample of the proband was used to perform whole-exome sequencing (WES) to explore the possible genetic causes of this disease. Postsequencing bioinformatic analyses and Sanger sequencing were conducted to verify the identified variants and parental origins on all family members in the pedigree. Results. By postsequencing bioinformatic analyses and Sanger sequencing, we identified a novel missense variant (NM_003722.4:c.948G>A; p.Met316Ile) of TP63 in this family that results in a substitution of methionine with isoleucine, which is probably associated with the occurrence of SHFM. Conclusion. A novel missense variant (NM_003722.4:c.948G>A; p.Met316Ile) of TP63 in SHFM was thus identified, which may enlarge the spectrum of known TP63 variants and also provide new approaches for genetic counselling of families with SHFM.

Probable Novel PSEN1 Gln222Leu Mutation in a Chinese Family with Early-Onset Alzheimer's Disease

2019 ◽  
Vol 16 (8) ◽  
pp. 764-769 ◽  
Author(s):  
Huayuan Wang ◽  
Ruihua Sun ◽  
Yingying Shi ◽  
Mingrong Xia ◽  
Jing Zhao ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Missense Mutation ◽  
Early Onset ◽  
Sanger Sequencing ◽  
Pathogenic Mutation ◽  
Presenilin 1 ◽  
Chinese Family ◽  
Whole Exome ◽  
Early Onset Alzheimer’S Disease

Background: The rate of occurrence of Alzheimer’s disease is increasing around the world. However, there is still no significant breakthrough in the study of its etiology and pathogenesis. Objective: To screen Alzheimer's disease pathogenic genes, which may be conducive to the elucidation of the pathogenic mechanisms of Alzheimer's disease And predict the pathogenicity by various computer software. Method: Clinical and neuroimaging examination, Whole Exome Sequencing, and Sanger sequencing were performed in the proband. Mutation sites were verified in 158 subjects. Results: We reported a proband carrying a probably novel pathogenic mutation, which clinically manifests as progressive memory loss, visual-spatial disorders, apraxia, psychobehavioral disorders, and temperamental and personality changes. Whole Exome Sequencing detected a novel missense mutation at codon 222 (Q222L), which is a heterozygous A to T point mutation at position 665 (c.665A>T) in exon 5 of the presenilin 1 leading to a glutamine-to-leucine substitution. The mutation was also identified by Sanger sequencing in one family member; nevertheless, it was not detected in the other 7 unaffected family members, 50 sporadic Alzheimer's disease patients and 100 control subjects. Conclusion: A novel mutation in exon 5 of the presenilin 1 gene (Gln222Leu) in a Chinese family with early-onset Alzheimer’s disease has been reported, besides， it was predicted that the missense mutation was probably a novel pathogenic mutation that was reported for the first time in a Chinese family with early-onset Alzheimer’s disease.

scholarly journals First Report ofCTNSMutations in a Chinese Family with Infantile Cystinosis

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Yong-jia Yang ◽  
Yuan Hu ◽  
Rui Zhao ◽  
Xinyu He ◽  
Liu Zhao ◽  
...  
Keyword(s):  
Chinese Population ◽  
Mutation Screening ◽  
Donor Site ◽  
Autosomal Recessive Disorder ◽  
Chinese Family ◽  
Acceptor Site ◽  
Ethnic Populations ◽  
Whole Exome ◽  
Infantile Cystinosis ◽  
Lysosomal Transport

Infantile cystinosis (IC) is a rare autosomal recessive disorder characterized by a defect in the lysosomal-membrane transport protein, cystinosin. It serves as a prototype for lysosomal transport disorders. To date, severalCTNSmutations have been identified as the cause of the prototypic disease across different ethnic populations worldwide. However, in Asia, theCTNSmutation is very rarely reported. For the Chinese population, no literature onCTNSmutation screening for IC is available to date. In this paper, by using the whole exome sequencing and Sanger sequencing, we identified two novelCTNSsplicing deletions in a Chinese IC family, one at the donor site of exon 6 ofCTNS(IVS6+1, del G) and the other at the acceptor site of exon 8 (IVS8-1, del GT). These data give information for the genetic counseling of the IC that occurred in Chinese population.

scholarly journals Two novel mutations in PRPF3 causing autosomal dominant retinitis pigmentosa

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Zilin Zhong ◽  
Min Yan ◽  
Wan Sun ◽  
Zehua Wu ◽  
Liyun Han ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Chinese Population ◽  
Sanger Sequencing ◽  
Autosomal Dominant ◽  
Photoreceptor Cells ◽  
Eye Diseases ◽  
Novel Mutations ◽  
Whole Exome ◽  
Selective Death ◽  
Exon 11

Abstract Retinitis pigmentosa (RP) is a heterogeneous set of hereditary eye diseases, characterized by selective death of photoreceptor cells in the retina, resulting in progressive visual impairment. Approximately 20–40% of RP cases are autosomal dominant RP (ADRP). In this study, a Chinese ADRP family previously localized to the region between D1S2819 and D1S2635 was sequenced via whole-exome sequencing and a variant c.1345C > G (p.R449G) was identified in PRPF3. The Sanger sequencing was performed in probands of additional 95 Chinese ADRP families to investigate the contribution of PRPF3 to ADRP in Chinese population and another variant c.1532A > C (p.H511P) was detected in one family. These two variants, co-segregate with RP in two families respectively and both variants are predicted to be pathological. This is the first report about the spectrum of PRPF3 mutations in Chinese population, leading to the identification of two novel PRPF3 mutations. Only three clustered mutations in PRPF3 have been identified so far in several populations and all are in exon 11. Our study expands the spectrum of PRPF3 mutations in RP. We also demonstrate that PRPF3 mutations are responsible for 2.08% of ADRP families in this cohort indicating that PRPF3 mutations might be relatively rare in Chinese ADRP patients.

scholarly journals Whole-exome sequencing identified a novel heterozygous mutation of SALL1 and a new homozygous mutation of PTPRQ in a Chinese family with Townes-Brocks syndrome and hearing loss

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Guangxian Yang ◽  
Yi Yin ◽  
Zhiping Tan ◽  
Jian Liu ◽  
Xicheng Deng ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
Nonsyndromic Hearing Loss ◽  
Whole Exome ◽  
Renal Malformations

Abstract Background Previous studies have revealed that mutations of Spalt Like Transcription Factor 1 (SALL1) are responsible for Townes-Brocks syndrome (TBS), a rare genetic disorder that is characterized by an imperforate anus, dysplastic ears, thumb malformations and other abnormalities, such as hearing loss, foot malformations, renal impairment with or without renal malformations, genitourinary malformations, and congenital heart disease. In addition, the protein tyrosine phosphatase receptor type Q (PTPRQ) gene has been identified in nonsyndromic hearing loss patients with autosomal recessive or autosomal dominant inherited patterns. Methods A Chinese family with TBS and hearing loss was enrolled in this study. The proband was a two-month-old girl who suffered from congenital anal atresia with rectal perineal fistula, ventricular septal defect, patent ductus arteriosus, pulmonary hypertension (PH), and finger deformities. The proband’s father also had external ear deformity with deafness, toe deformities and PH, although his anus was normal. Further investigation found that the proband’s mother presented nonsyndromic hearing loss, and the proband’s mother’s parents were consanguine married. Whole-exome sequencing and Sanger sequencing were applied to detect the genetic lesions of TBS and nonsyndromic hearing loss. Results Via whole-exome sequencing and Sanger sequencing of the proband and her mother, we identified a novel heterozygous mutation (ENST00000251020: c.1428_1429insT, p. K478QfsX38) of SALL1 in the proband and her father who presented TBS phenotypes, and we also detected a new homozygous mutation [ENST00000266688: c.1057_1057delC, p. L353SfsX8)] of PTPRQ in the proband’s mother and uncle, who suffered from nonsyndromic hearing loss. Both mutations were located in the conserved sites of the respective protein and were predicted to be deleterious by informatics analysis. Conclusions This study confirmed the diagnosis of TBS at the molecular level and expanded the spectrum of SALL1 mutations and PTPRQ mutations. Our study may contribute to the clinical management and genetic counselling of TBS and hearing loss.

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