scholarly journals Recurrent PAX 6 mutation in a Chinese family with congenital aniridia, progressive cataracts and mental retardation

2018 ◽  
Vol 30 (1) ◽  
pp. 181-188
Author(s):  
Dou-Dou Chen ◽  
Tao Yang ◽  
Si-Quan Zhu
Keyword(s):  
Mental Retardation ◽  
Family Members ◽  
Gene Mutations ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Pathological Feature ◽  
Phosphate Backbone ◽  
Symptom Complex ◽  
Congenital Aniridia ◽  
And Control

Background: One prominent pathological feature of congenital aniridia is hypoplasia of the iris, often accompanied by other eye abnormalities. The objective of this study is to identify gene mutations responsible for autosomal dominance in a Chinese family with congenital aniridia, progressive cataracts and mental retardation. Methods: A total of 11 family members, including 6 affected and 5 unaffected individuals were recruited. Whole exome sequencing was performed on the proband and Sanger sequencing was applied to identify the causal mutation in the other family members and control samples. Results: A heterozygous mutation, c. 112delC (p. Arg38fs) in PAX 6, was identified in the family that was associated with congenital aniridia, progressive cataracts and mental retardation. The mutation was exclusively observed in all affected individuals but not in unaffected family members or unrelated healthy controls without aniridia recruited from Beijing Tongren Hospital. Bioinformatics analysis indicated that the mutation c. 112delC (p. Arg38fs) in PAX 6 affected sugar phosphate backbone construction, leading to half reduction of the full-length protein. Other symptoms such as lens opacity, keratitis, lens dislocation, ciliary body hypoplasia, foveal hypoplasia and mental development retardation were also observed in this family. Conclusion: These results provided a new insight into the effects of PAX 6 as a mutational hotspot, with a symptom complex that includes congenital aniridia, progressive cataracts and mental retardation. These findings suggested the cognitive treatment of PAX 6-mutated individuals could be considered earlier clinically, combined with medication or surgery of congenital aniridia and progressive cataracts.

Analysis of the JAK2 Gene cDNA Full-Length In One Chinese Familial Myeloproliferative Disorders

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5056-5056
Author(s):  
Ru Feng ◽  
Lixia Hao ◽  
Yongmin Zhang ◽  
Yongqiang Wei ◽  
Fen Huang ◽  
...  
Keyword(s):  
Family Members ◽  
Gene Mutations ◽  
Myeloproliferative Disorders ◽  
Full Length ◽  
The Other ◽  
Jak2v617f Mutation ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
The Family

Abstract Abstract 5056 Introduction: JAK2V617F point mutation have been confirmed to be one of the major molecular mechanism of BCR/ABL negative myeloproliferative disorders(MPD). Besides, some other gene mutations such as JAK2 exon12, MPL W515L/K, c-mpl and EPOR have extended the scope of the research in this field. Most of the MPD patients are sporadic and there are seldom reports in Chinese familial MPD. 2008 ASH metting we have reported in a Chinese family of MPD's findings, the two brothers in our hospital diagnosis for MPD (one is a PV, another is ET), then we investigated the 15 members of the family. We discovered that there were three male members carried the JAK2V617F mutation in this family, including the two MPD patients and their father, which affected in two generations. All the family members were confirmed as BCR/ABL, MPL W515L/K, c-mpl, and EPOR negative. Subsequently, in order to understand the existence of family members in addition to the gene JAK2 V617F mutation, the existence of JAK2 gene mutations in other parts of the? if other mutations in existence and the high incidence of family members of MPD? We focus on the cDNA full-length of JAK2 gene to provide some theory basis on the pathogenesis in MPD. Methods: A total of 15 family members were enrolled in our study, including 2 brothers of MPD patients (the older one was thrombocythemia (ET), and another is polycythemia vera (PV)) and the other members in the same family. The mRNA of mononuclear cells from peripheral blood sample was extracted according to the manufacturer's instruction (TAKARA). RT-PCR and DNA sequencing have been used to analyze the cDNA full-length of the JAK2 gene. Results: All of the samples can be analyzed for JAK2 cDNA full-length. 3 members carried the JAK2V617F mutation (1849G®T) in this family, including the two MPD patients and their father. And the older brother was homozygous mutation and the other two were heterozygous mutation. All of the 15 samples were JAK2 exon12 gene mutation negative. 2 persons who were the male ET patient's children had a heterozygous mutation (380G®A) in JAK2 exon 3, caused a glycine-to-asparticacid substitution at position 127. Besides, 13 persons had 489C®T mutation in exon 4 and 14 persons had 2490G→A mutation in exon 17 in this family, But they were both same-sense mutation. Conclusion: It is necessary to do routine analysis of blood and other related inspection for MPD patient's family members, so as to make diagnosis earlier. However, we are not sure that the sequencing results are unique to all the familial MPD and need to be confirmed by more cases. We still do not determine the current discovery point mutations have biological significance, still need to be further explored. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Novel missense mutation of SASH1 in a Chinese family with dyschromatosis universalis hereditaria

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Lu Cao ◽  
Ruixue Zhang ◽  
Liang Yong ◽  
Shirui Chen ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Sequence Alignment ◽  
Multiple Sequence Alignment ◽  
Molecular Genetic ◽  
Family Members ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Mendelian Inheritance ◽  
Chinese Family ◽  
Multiple Sequence

Abstract Background Dyschromatosis universalis hereditaria (DUH) is a pigmentary dermatosis characterized by generalized mottled macules with hypopigmention and hyperpigmention. ABCB6 and SASH1 are recently reported pathogenic genes related to DUH, and the aim of this study was to identify the causative mutations in a Chinese family with DUH. Methods Sanger sequencing was performed to investigate the clinical manifestation and molecular genetic basis of these familial cases of DUH, bioinformatics tools and multiple sequence alignment were used to analyse the pathogenicity of mutations. Results A novel missense mutation, c.1529G>A, in the SASH1 gene was identified, and this mutation was not found in the National Center for Biotechnology Information Database of Short Genetic Variation, Online Mendelian Inheritance in Man, ClinVar, or 1000 Genomes Project databases. All in silico predictors suggested that the observed substitution mutation was deleterious. Furthermore, multiple sequence alignment of SASH1 revealed that the p.S510N mutation was highly conserved during evolution. In addition, we reviewed the previously reported DUH-related gene mutations in SASH1 and ABCB6. Conclusion Although the affected family members had identical mutations, differences in the clinical manifestations of these family members were observed, which reveals the complexity of the phenotype-influencing factors in DUH. Our findings reveal the mutation responsible for DUH in this family and broaden the mutational spectrum of the SASH1 gene.

A Novel 4.25kb Deletion in PAX6 in A Chinese Han Family with Congenital Aniridia Combined with Cataract and Nystagmus

2021 ◽  
Author(s):  
Tianwei Qian ◽  
Chong Chen ◽  
Caihua Li ◽  
Qiaoyun Gong ◽  
Kun Liu ◽  
...  
Keyword(s):  
Genetic Defect ◽  
Family Members ◽  
Anterior Segment ◽  
Chinese Family ◽  
The Novel ◽  
Slit Lamp ◽  
Heterozygous Deletion ◽  
Chinese Han ◽  
Normal People ◽  
Congenital Aniridia

Abstract Background: The aim of this study is to identify the genetic defect in a Chinese family with congenital aniridia combined with cataract and nystagmus.Methods: Complete ophthalmic examinations, including slit-lamp biomicroscopy, dilatedindirect ophthalmoscopy, anterior segment photography, and anterior segment optical coherence tomography (OCT) were performed. Blood samples were collected from all family members and genomic DNA was extracted. Genome sequencing was performed in all family members and Sanger sequencing was used to verify variant breakpoints.Results: All the thirteen members in this Chinese family, including seven patients and six normal people, were recruited in this study. The ophthalmic examination of affected patients in this family was consistent with congenital aniridia combined with cataract and nystagmus. A novel heterozygous deletion (NC_000011.10:g.31802307_31806556del) containing the 5’ region of PAX6 gene was detected that segregated with the disease. Conclusion: We detected a novel deletion in PAX6 responsible for congenital aniridia in the affected individuals of this Chinese family. The novel 4.25kb deletion in PAX6 gene of our study would further broaden the genetic defects of PAX6 associated with congenital aniridia.

SOX2 heterozygous mutation causes multiple extra-ocular phenotypes in boys

2020 ◽  
Author(s):  
Yi Wang ◽  
LiJun Fan ◽  
Xiaoya Ren ◽  
Yanning Song ◽  
Beibei Zhang ◽  
...  
Keyword(s):  
Mental Retardation ◽  
De Novo ◽  
Hypogonadotropic Hypogonadism ◽  
Gene Mutations ◽  
Delayed Puberty ◽  
Heterozygous Mutation ◽  
Common Symptom ◽  
Causative Gene ◽  
Pathogenic Genes ◽  
The Central Nervous System

Abstract Background The SOX2 gene is widely expressed in the eyes and the central nervous system. Heterozygous mutations could cause eye malformations and hypopituitarism, and serve as the causative gene for syndromic and non-syndromic hypogonadotropic hypogonadism (HH). Our study reports three children with chromosome 46, XY, SRY (+), but SOX2 mutations.Methods Three children visited our endocrine clinic because of micropenis and/or cryptorchidism. Clinical data were collected, and one took PANEL sequencing and the others for whole exome sequencing. Then we summarized characteristics of the patients and compared with those mentioned in literature.Results Patient 1 manifested with micropenis, patient 2 with bilateral cryptorchidism and craniofacial deformities, both carrying the same reported SOX2 gene mutation (T232N), and both mutations from mothers with delayed puberty only. Patient 3 showed micropenis, mental retardation and craniofacial deformities, and the child carried a spontaneous truncation mutation (Y110X) of the SOX2 gene. This site has reported that a missense mutation caused adolescent adolescence without major eye signs. All three patients carried another gene mutations that affected hypothalamic-pituitary function: Patient 1, FGFR1: c.238C>T/p.R80C (uncertain) from father; Patient 2, CHD7: c.2656C>T/p.R886W (pathogenic) de novo; Patient 3, SEMA3A: c.1432G> A/p.E478K (uncertain) from mother. None had major ocular malformations, and all showed genitourinary tract malformations. Two patients had craniofacial deformities, and one patient had muscle anomality and intellectual disability. We summarized previous studies with SOX2 gene mutations and it showed: 71.2% of mutations are de novo, all patients reported whose variants inherit from parents, 15.1% parents (including mother 11.0% and father 4.1%) show completely normal phenotypes, 4.1% (3/73) variants inherit from mother with germinal mosaicism. Except for major ocular malformations (91.1%), the most common phenotype is developmental delay/mental retardation (DD/MR), accounting for 40.7%, followed by brain anomely (BA), accounting for 28.5%, male genital abnormalities (GA) for 20.3%, non-syndromic HH accounted for 4.9%, the younger the patients visit the doctor, the more common the retardation are. Conclusion SOX2 mutations could cause a broad phenotype spectrum from completely normal to severe ocular malformations, retardation and most mutations are de novo. Except for major ocular malformations and retardation, GA/HH is another common symptom. GA/HH may be the only symptom, and SOX2 may cooperate with another HH pathogenic genes to cause non-syndromic HH.

scholarly journals A Novel CRYBB2 Stopgain Mutation Causing Congenital Autosomal Dominant Cataract in a Chinese Family

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yu Zhou ◽  
Yaru Zhai ◽  
Lulin Huang ◽  
Bo Gong ◽  
Jie Li ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Congenital Cataract ◽  
Autosomal Dominant ◽  
Family Members ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Whole Exome ◽  
Causal Mutation ◽  
Control Samples

Congenital cataract is the most common cause of the visual disability and blindness in childhood. This study aimed to identify gene mutations responsible for autosomal dominant congenital cataract (ADCC) in a Chinese family using next-generation sequencing technology. This family included eight unaffected and five affected individuals. After complete ophthalmic examinations, the blood samples of the proband and two available family members were collected. Then the whole exome sequencing was performed on the proband and Sanger sequencing was applied to validate the causal mutation in the two family members and control samples. After the whole exome sequencing data were filtered through a series of existing variation databases, a heterozygous mutation c.499T<G (p.E167X) in CRYBB2 gene was found. And the results showed that the mutation cosegregated with the disease phenotype in the family and was absolutely absent in 1000 ethnicity-matched control samples. Thus, the heterozygous mutation c.499T<G (p.E167X) in CRYBB2 was the causal mutation responsible for this ADCC family. In conclusion, our findings revealed a novel stopgain mutation c.499T<G (p.E167X) in the exon 6 of CRYBB2 which expanded the mutation spectrum of CRYBB2 in Chinese congenital cataract population and illustrated the important role of CRYBB2 in the genetics research of congenital cataract.

scholarly journals A KRT6A mutation p.Ile462Asn in a Chinese family with pachyonychia congenita, and identification of maternal mosaicism: a case report

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yue Li ◽  
Yumeng Wang ◽  
Yan Ming ◽  
Pan Chaolan ◽  
Zhang Jia ◽  
...  
Keyword(s):  
Low Frequency ◽  
Gene Mutations ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Low Grade ◽  
Palmoplantar Keratoderma ◽  
Autosomal Dominant Disorder ◽  
Keratin Gene ◽  
Nail Discoloration ◽  
Pachyonychia Congenita

Abstract Background Pachyonychia congenita (PC, OMIM #167200, #167210, #615726, #615728, and #615735) is a rare autosomal dominant disorder caused by keratin gene mutations in KRT6A,KRT6B,KRT6C,KRT16 or KRT17. It is characterized with nail dystrophy and palmoplantar keratoderma (PPK). The most prominent manifestation is plantar pain. This is a further unusual case of parental mosaicism in PC. Although very rare, germ cell mosaicism should be considered when providing genetic counselling for unaffected parents of a child with PC. Case presentation We report the case of a 5-year-old boy with thickening nails and oral leukokeratosis at birth. He began to develop palmoplantar keratoderma at 2 years old and his sister has similar clinical manifestation characterized with nail discoloration and thickening. A previously reported heterozygous mutation, p.Ile462Asn, was identified in KRT6A in the proband and his affected sister. SNaPshot sequencing revealed mosaicism at a level of 2.5% and 4.7% in DNA from blood and hair bulbs from the unaffected mother. HiSeq deep sequencing demonstrated low-grade mosaicism in the patient’s younger sister and parents. Conclusion These findings indicate the ability of WES and SNaPshot sequencing to detect low-frequency mosaic mutations. Although very rare, germinal mosaicism should be considered when genetic counseling is given to families with presumed spontaneous cases of PC.

scholarly journals Novel Genetic Findings in a Chinese Family with Axenfeld-Rieger Syndrome

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Kuanshu Li ◽  
Liu Yang ◽  
Ying Liu ◽  
Ding Lin
Keyword(s):  
Genetic Counseling ◽  
Genetic Analysis ◽  
Gene Mutation ◽  
Genomic Dna ◽  
Gene Mutations ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
Specific Therapy ◽  
Rieger Syndrome

Purpose. To describe a Chinese family with Axenfeld-Rieger syndrome (ARS) and report our novel genetic findings.Methods. Nine members of the same family underwent complete ophthalmologic examinations and genetic analysis. Genomic DNA was isolated from veinal blood and amplifed using PCR; the products of PCR were sequenced and compared with FOXC1 and PITX2 genes, from which the mutations were found.Results. Through the ophthalmologic examinations, 8 subjects were diagnosed as ARS and 1 subject was normal. A homozygous mutation c.1139_1141dupGCG(p.Gly380_Ala381insGly) and a heterozygous mutation c.1359_1361dupCGG(p.Gly456_Gln457insGly) in FOXC1 were identified in all subjects. The mutation (c.-10-30T>C) was identified in PITX2 in subjects III-1 and III-3.Conclusions.We found novel gene mutations in a Chinese family with ARS, which provides us with a better understanding of the gene mutation spectrum of ARS and the assistance for the genetic counseling and gene-specific therapy in the future.

scholarly journals Heterozygous RHO p.R135W missense mutation in a large Han-Chinese family with retinitis pigmentosa and different refractive errors

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Yuan Wu ◽  
Yi Guo ◽  
Junhui Yi ◽  
Hongbo Xu ◽  
Lamei Yuan ◽  
...  
Keyword(s):  
Retinitis Pigmentosa ◽  
Missense Mutation ◽  
Family Members ◽  
Gene Mutations ◽  
Clinical Findings ◽  
Han Chinese ◽  
Chinese Family ◽  
Refractive Errors ◽  
Epiretinal Membranes ◽  
Target Gene Therapy

Abstract Retinitis pigmentosa (RP), the most common type of inherited retinal degeneration causing blindness, initially manifests as severely impaired rod function followed by deteriorating cone function. Mutations in the rhodopsin gene (RHO) are the most common cause of autosomal dominant RP (adRP). The present study aims to identify the disease-causing mutation in a numerous, four-generation Han-Chinese family with adRP detected by whole exome sequencing and Sanger sequencing. Afflicted family members present classic adRP along with heterogeneous clinical phenotypes including differing refractive errors, cataracts, astigmatism and epiretinal membranes. A missense mutation, c.403C>T (p.R135W), in the RHO gene was identified in nine subjects and it co-segregated with family members. The mutation is predicted to be disease-causing and results in rhodopsin protein abnormalities. The present study extends the genotype–phenotype relationship between RHO gene mutations and adRP clinical findings. The results have implications for familial genetic counseling, clinical management and developing RP target gene therapy strategies.

A Novel PAX6 Heterozygous Mutation Found in a Chinese Family with Congenital Aniridia

2019 ◽  
Vol 23 (7) ◽  
pp. 495-500 ◽  
Author(s):  
Ying Xiao ◽  
Xiangqin Liu ◽  
Chen Yang ◽  
Liping Liu ◽  
Xiaoxin Guo ◽  
...  
Keyword(s):  
Chinese Family ◽  
Heterozygous Mutation ◽  
Congenital Aniridia

scholarly journals A novel 4.25 kb heterozygous deletion in PAX6 in a Chinese Han family with congenital aniridia combined with cataract and nystagmus

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tianwei Qian ◽  
Chong Chen ◽  
Caihua Li ◽  
Qiaoyun Gong ◽  
Kun Liu ◽  
...  
Keyword(s):  
Genetic Defect ◽  
Family Members ◽  
Anterior Segment ◽  
Chinese Family ◽  
The Novel ◽  
Heterozygous Deletion ◽  
Chinese Han ◽  
Indirect Ophthalmoscopy ◽  
Normal People ◽  
Congenital Aniridia

Abstract Background The aim of this study is to identify the genetic defect in a Chinese family with congenital aniridia combined with cataract and nystagmus. Methods Complete ophthalmic examinations, including slit-lamp biomicroscopy, dilated indirect ophthalmoscopy, anterior segment photography, and anterior segment optical coherence tomography (OCT) were performed. Blood samples were collected from all family members and genomic DNA was extracted. Genome sequencing was performed in all family members and Sanger sequencing was used to verify variant breakpoints. Results All the thirteen members in this Chinese family, including seven patients and six normal people, were recruited in this study. The ophthalmic examination of affected patients in this family was consistent with congenital aniridia combined with cataract and nystagmus. A novel heterozygous deletion (NC_000011.10:g.31802307_31806556del) containing the 5′ region of PAX6 gene was detected that segregated with the disease. Conclusion We detected a novel deletion in PAX6 responsible for congenital aniridia in the affected individuals of this Chinese family. The novel 4.25 kb deletion in PAX6 gene of our study would further broaden the genetic defects of PAX6 associated with congenital aniridia.

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