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.

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.

Two siblings with metachromatic leukodystrophy caused by a novel identified homozygous mutation in the ARSA gene

2018 ◽  
Vol 31 (9) ◽  
pp. 1047-1051 ◽  
Author(s):  
Mahmut Aslan ◽  
Serkan Kirik ◽  
Bilge Özgör ◽  
Serdal Güngör
Keyword(s):  
Genetic Analysis ◽  
Metachromatic Leukodystrophy ◽  
Genetic Diagnosis ◽  
Gene Mutations ◽  
Heterozygous Mutation ◽  
Homozygous Mutation ◽  
Inherited Disease ◽  
Normal Ranges ◽  
Clinical Presentations ◽  
The One

Abstract Background Metachromatic leukodystrophy (MLD) is an autosomal recessively (AR) inherited disease caused by the deficiency of the enzyme arylsulfatase A (ARSA). Although MLD is the most common form of hereditary leukoencephalopathy, it is still very rare. More than 200 gene mutations have been identified in the ARSA gene. The most frequently identified mutation is the one located on chromosome 22q13.33. In the present study, new mutations are reported in two siblings of different ages and with different clinical presentations. Case presentation A 9-year-old male patient, suffering from ataxia, attention deficit and perceptual difficulties, was first seen at the age of 7. While the findings of neurological examination and neuroradiological evaluation suggested MLD, the ARSA enzyme levels were analyzed and found to be at a lower limit. Genetic analysis revealed variant homozygous mutations of the ARSA gene at p.N352S/c.1055T>C in exon 6 and at p.E331K/c.991G>A in exon 7. In the genetic analysis of his three siblings and parents, a variant heterozygous mutation of the ARSA gene was detected at p.N352S/c.1055T>C in exon 6 and at p.E331K/c.991G>A in exon 7. Conclusions MLD is a rare disease; however, it is likely to find different variant forms in our population, in which the frequency of consanguineous marriages is high. Genetic diagnosis is important in symptomatic cases with enzyme levels within the normal ranges.

scholarly journals A severe recessive and a mild dominant form of Charcot-Marie-Tooth disease associated with a newly identified Glu222Lys GDAP1 gene mutation.

2014 ◽  
Vol 61 (4) ◽  
Author(s):  
Dagmara Kabzińska ◽  
Katarzyna Kotruchow ◽  
Joanna Cegielska ◽  
Irena Hausmanowa-Petrusewicz ◽  
Andrzej Kochański
Keyword(s):  
Genetic Counseling ◽  
Gene Mutation ◽  
Autosomal Dominant ◽  
Clinical Course ◽  
Axonal Neuropathy ◽  
Gene Mutations ◽  
Special Importance ◽  
Recessive Trait ◽  
Dominant Form ◽  
Charcot Marie Tooth

Charcot-Marie-Tooth (CMT) disease caused by mutations in the GDAP1 gene has been shown to be inherited via traits that may be either autosomal recessive (in the majority of cases) [CMT4A] or autosomal dominant [CMT2K]. CMT4A disease is characterized by an early onset, and a severe clinical course often leading to a loss of ambulation, whereas CMT2K is characterized by a mild clinical course of benign axonal neuropathy beginning even in the 6th decade of life. Clinical data from a GDAP1 mutated patient suggests that the presence of a particular mutation is associated with a certain trait of inheritance. The association of a particular GDAP1 gene mutation and a dominant or recessive trait of inheritance is of special importance for genetic counseling and the prenatal diagnostics as regards severe forms of CMT. In the present study we report on two CMT families in which a newly identified Glu222Lys mutation within the GDAP1 gene segregates both in autosomal dominant and recessive traits. Our study shows that at least some GDAP1 gene mutations may segregate with the CMT phenotype as both dominant and recessive traits. Thus, genetic counseling for CMT4A/CMT2K families requires more extensive data on GDAP1 phenotype-genotype correlations.

scholarly journals BETA-GLOBIN GENE MUTATIONS IN TURKISH CHILDREN WITH BETA-THALASSEMIA: RESULTS FROM A SINGLE CENTER STUDY

2013 ◽  
Vol 5 (1) ◽  
pp. e2013055 ◽  
Author(s):  
Ali Fettah ◽  
Cengiz Bayram ◽  
Nese Yarali ◽  
Pamir Isik ◽  
Abdurrahman Kara ◽  
...  
Keyword(s):  
Globin Gene ◽  
Gene Mutations ◽  
Thalassemia Major ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Thalassemia Intermedia ◽  
Turkish Children ◽  
Tertiary Center

Introduction: The beta thalassemias are common genetic disorders in Turkey and in this retrospective study our aim was to evaluate β-globin chain mutations and the phenotypic severity of β-thalassemia patients followed-up in our hospital, a tertiary center which serves patients from all regions of Turkey. Materials and Methods: 106 pediatric patients were analysed for β-globin gene mutations by using DNA analysis. Patients were classified as having β-thalassemia major or β-thalassemia intermedia based on age at diagnosis, transfusion frequency and lowest hemoglobin concentration in between transfusions. Results: There were 106 patients (52.8% female and 47.2% male) with a mean age of 11.2±5 years (1.6 – 22.3 years). Eighty-four (79.2%) patients had β-thalassemia major, whereas the remaining 22 patients (20.8%) were identified as having β-thalassemia intermedia. Overall, 18 different mutations were detected on 212 alleles. The most frequently encountered mutation was IVS I.110 (G>A) (35.3%), followed by Codon 8 del-AA (10.4%), IVS II.1 (G>A) (8%), IVS I.1 (G>A) (7.5%), Codon 39 (C>T) (7.1%) and Codon 5 (-CT) (6.6%), which made up 79.4% of observed mutations. According to present results, IVS I.110 (G>AA) was the most frequent mutation observed in this study, as in other results from Turkey. Evaluation of β-thalassemia mutations in 106 patients with 212 alleles, revealed the presence of homozygous mutation in 85 patients (80.2%) and compound heterozygous mutation in 21 patients (19.8%). The mutations detected in patients with homozygous mutation were IVS I.110 (G>A) (38.8%), Codon 8 del –AA (11.8%), IVS II.1 (G>A) (8.2%) and IVS I.1 (G>A) (8.2%). Observed mutations in the compound heterozygotes were Codon 39 (C>T)/Codon 41-42 (-CTTT) (14.3%), IVS I.110 (G>A)/Codon 39(C>T) (14.3%), IVS I.110 (G>A)/Codon 44(-C) (14.3%), and IVS II.745 (C>G)/ 5’UTR + 22 (G>A) (9.5%). Conclusion: Our hospital is a tertiary referral center that provides care to patients from all over the country, and thus the distribution of mutations observed in the current study is significant in term of representing that of the country as a whole.

scholarly journals New macular findings in individuals with biallelic KLHL7 gene mutation

2019 ◽  
Vol 4 (1) ◽  
pp. e000234 ◽  
Author(s):  
Ling Zhi Heng ◽  
Joanna Kennedy ◽  
Sarah Smithson ◽  
Ruth Newbury-Ecob ◽  
Amanda Churchill
Keyword(s):  
Young Adults ◽  
Gene Mutation ◽  
Late Onset ◽  
Protein A ◽  
Retinal Dystrophy ◽  
Gene Mutations ◽  
Photoreceptor Cells ◽  
Ubiquitin Proteasome System ◽  
Proper Function ◽  
Homozygous Mutation

ObjectiveThe ubiquitin-proteasome system pathway has been recognised as a crucial cellular mechanism for the proper function of photoreceptor cells. In particular, ubiquitin ligases (E3s) recognise and ubiquitinate specific proteins for degradation. The KLHL7 protein (a BTB-Kelch protein) has been found to play an important role in this process. There have been several reports that heterozygous mutations in the KLHL7 gene in adults are responsible for a rare cause of late-onset autosomal dominant retinitis pigmentosa with preservation of central vision and homozygous mutations in two young children, with Crisponi syndrome (CS)/cold-induced sweating syndrome type 1, result in a recessive form of early-onset peripheral retinal dystrophy type changes. The majority of children do not survive through to adulthood. The objective of this study is to report the visual symptoms and signs of two young adults clinically diagnosed with overlapping BOS/Cisproni syndrome, expanding the phenotypic presentation of KLHL7 gene mutations.Methods and analysisThis is a case report of the ophthalmic findings of two siblings with biallelic KLHL7 gene mutations. Siblings born to a non-consanguineous family and diagnosed with the overlapping clinical phenotype of Bohring-Opitz and and confirmed biallelic KLHL 7 gene mutation by whole exome sequencing were identified. Ophthlamic history and fundal examination was performed and analysed.ResultsBoth patients had similar retinal findings. The fundus shows confluent hypopigmented/pale yellow lesions in the mid-periphery. The optic disc appears to be pale with a ring of atrophy and vessels appear attenuated. The macular of the younger patient shows a depigmented area around the fovea giving a bull’s-eye appearance while the older sibling shows a fibrotic ring around the fovea suggesting a more advanced pathology.ConclusionThis paper expands the retinal phenotype to include a distinctive maculopathy in a recently described homozygous mutation in the KLHL7 gene in two young adults presenting with features that overlap the Bohring-Opitz syndrome and CS.

scholarly journals Early Onset of Combined Oxidative Phosphorylation Deficiency in Two Chinese Brothers Caused by a Homozygous (Leu275Phe) Mutation in the C1QBP Gene

2020 ◽  
Vol 8 ◽  
Author(s):  
Jie Wang ◽  
Huan Li ◽  
Min Sun ◽  
Ying Yang ◽  
Qianli Yang ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Early Onset ◽  
Autosomal Recessive ◽  
Clinical Laboratory ◽  
Clinical Manifestations ◽  
Hereditary Diseases ◽  
Exercise Intolerance ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Homozygous Mutation

Mitochondrial diseases constitute a group of heterogeneous hereditary diseases caused by impairments in mitochondrial oxidative phosphorylation and abnormal cellular energy metabolism. C1QBP plays an important role in mitochondrial homeostasis. In this study, clinical, laboratory examinations, 12-lead electrocardiographic, ultrasonic cardiogram, and magnetic resonance imaging data were collected from four members of a Chinese family. Whole exome were amplified and sequenced for the proband. The structure of protein encoded by the mutation was predicted using multiple software programs. The proband was a 14-year old boy with myocardial hypertrophy, exercise intolerance, ptosis, and increased lactate. His 9-year old brother exhibited similar clinical manifestations while the phenomenon of ptosis was not as noticeable as the proband. The onset of this disease was in infancy in both cases. They were born after uneventful pregnancies of five generation blood relative Chinese parents. A homozygous mutation (Leu275Phe) in the C1QBP gene was identified in both brothers in an autosomal recessive inherited pattern. Their parents were heterozygous mutation carriers without clinical manifestations. We demonstrated that a homozygous C1QBP- P.Leu275Phe mutation in an autosomal recessive inherited mode of inheritance caused early onset combined oxidative phosphorylation deficiency 33 (COXPD 33) (OMIM:617713) in two brothers from a Chinese family.

scholarly journals A 12-Year-Old Girl with Bilateral Coats Disease and ABCA4 Gene Mutation

2018 ◽  
Vol 9 (2) ◽  
pp. 375-380 ◽  
Author(s):  
Ali Osman Saatci ◽  
Ziya Ayhan ◽  
Aylin Yaman ◽  
Elcin Bora ◽  
Ayfer Ulgenalp ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Gene Mutation ◽  
Laser Photocoagulation ◽  
Functional Result ◽  
Systemic Disease ◽  
Gene Mutations ◽  
Dexamethasone Implant ◽  
Single Session ◽  
Abca4 Gene ◽  
Coats Disease

A 12-year-old girl with bilateral stage 2B Coats disease was screened meticulously for a possible underlying systemic disease as she was female and the disease was bilateral. Full systemic workout turned out to be unremarkable. However, an ABCA4 gene mutation was found in the genetic analysis. NDP and TINF2 gene mutations were not present. She was successfully treated with a bilateral, single intravitreal injection of dexamethasone implant and a single session of indirect laser photocoagulation with a relatively good anatomic and functional result. To the best of our knowledge, the present case is the only reported case of Coats disease with an ABCA4 gene mutation.

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.

Familial hypophosphatemic rickets caused by a PHEX gene mutation accompanied by a NPR2 missense mutation

2020 ◽  
Vol 33 (2) ◽  
pp. 305-311
Author(s):  
Yongting Zhao ◽  
Fan Yang ◽  
Lihong Wang ◽  
Hui Che
Keyword(s):  
Gene Mutation ◽  
Age Of Onset ◽  
Gene Mutations ◽  
Hereditary Disease ◽  
Hypophosphatemic Rickets ◽  
Chinese Patients ◽  
Chinese Family ◽  
Dihydroxyvitamin D ◽  
Phex Gene ◽  
Urinary Phosphorus Excretion

AbstractBackgroundFamilial hypophosphatemic rickets, which is usually acknowledged as X-linked hypophosphatemic rickets (XLH), is a rare hereditary disease. XLH caused by mutations in the PHEX gene often manifests as growth retardation, skeletal deformities, osteodynia and dental dysplasia. NPR2 mutations are reported to cause disproportionate short stature. Our study was designed to identify the gene mutations of three patients in one family.Case descriptionA 40-year-old Chinese male visited the hospital for continuous osteodynia and presented with bilateral leg bowing, absent teeth and a progressive limp. The age of onset was approximately 2 years old. His 63-year-old mother and 42-year-old brother both shared identical symptoms with him. The laboratory tests were consistent with XLH, which showed decreased levels of blood phosphorus and 1,25-dihydroxyvitamin D3 as well as increased urinary phosphorus excretion. Mutation analysis revealed that the proband as well as his mother and his brother all had a PHEX mutation in exon 14 (c.1543C > T), and the proband also had a NPR2 mutation in exon 21 (c.3058C > T).ConclusionsWe report the familial hypophosphatemic rickets of three patients in a Chinese family caused by a PHEX gene mutation in exon 14 (c.1543C > T), which had never been reported in Chinese patients. We first report an XLH case together with a NPR2 mutation that had never been reported before.

scholarly journals β globin mutations in Turkish, Northern Iraqi and Albanian patients with β thalassemia major

2018 ◽  
Vol 8 (2) ◽  
Author(s):  
Veysel Sabri Hancer ◽  
Tunc Fisgin ◽  
Murat Buyukdogan ◽  
Ceyhun Bozkurt ◽  
Sotiraq Lako
Keyword(s):  
Genetic Counseling ◽  
Genomic Dna ◽  
Mutation Detection ◽  
Globin Gene ◽  
Venous Blood ◽  
Gene Mutations ◽  
Thalassemia Major ◽  
Target Dna ◽  
Frequent Allele ◽  
Pcr Genotyping

The mutation detection of β thalassemia is absolutely necessary for molecular diagnosis, as well as any genetic epidemiological study. The β globin gene has 3 exons and 2 introns, involved in β-thalassemic pathogenesis. The study aim of the study is to characterize the spectrum of β globin gene mutations in 136 Turkish, Northern Iraqi and Albanian pediatric β thalassemia major patients. After genomic DNA extraction from venous blood and amplification of the target DNA regions with PCR, genotyping was achieved by Sanger based DNA sequencing. The IVSI-110 G>A mutation was the most frequent allele in the Turkish and Albanian patients. In Northern Iraqi patients IVSI-1 G>A was is the most frequent. There are two mutations are firstly reported for Albania [c.*111 A>G 3’ UTR (rs63751128) and c.113 G>A (p.Trp38Ter, p.W38*) (rs35887507)] with this study. These findings may be of value for genetic counseling, premarital diagnosis, prenatal diagnosis and prevention programs.

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