The diagnosis of cystinosis in patients reveals new CTNS gene mutations in the Chinese population

2019 ◽  
Vol 32 (4) ◽  
pp. 375-382
Author(s):  
Xiao-Qiao Li ◽  
Di Wu ◽  
Xue-Jun Liang ◽  
Wen-Jing Li ◽  
Min Liu ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Growth And Development ◽  
Chinese Population ◽  
Autosomal Recessive ◽  
Gene Mutations ◽  
Autosomal Recessive Disorder ◽  
Diagnostic Procedures ◽  
Alternative Therapies ◽  
Novel Mutations ◽  
Chromosome 17P13

Abstract Background Cystinosis is a rare autosomal-recessive disorder caused by a defective transport of cystine across the lysosomal membrane. Previous studies have mapped cystinosis to the CTNS gene which is located on chromosome 17p13, and various CTNS mutations have been identified to correlate them with this disease. Methods We analyzed six patients from five unrelated families who were diagnosed with cystinosis in our hospital. We described the diagnostic procedures for all the patients and proposed alternative therapies for cystinosis patients instead of using cysteamine, an orphan drug which was commercially unavailable in China. Moreover, genetic analysis of all patients’ samples was carried out to identify novel CTNS gene mutations. Results and conclusions The patients in this study were followed up from 1 to more than 10 years to monitor their growth and development, which indicated that the alternative therapies we used were helpful to ameliorate the complications of the cystinosis patients without cysteamine. Furthermore, by sequencing the patients’ genome, we identified novel mutations in the CTNS gene including: c.477C > G (p.S159R), c.274C > T (p.Q92X) and c.680A > T (p.E227V); these mutations were only observed in cystinosis patients and had never been reported in any other populations, suggesting they might be specific to Chinese cystinosis patients.

scholarly journals Genetic and Molecular Evaluation: Reporting Three Novel Mutations and Creating Awareness of Pycnodysostosis Disease

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1552
Author(s):  
Khalda Sayed Amr ◽  
Hala T. El-Bassyouni ◽  
Sawsan Abdel Hady ◽  
Mostafa I. Mostafa ◽  
Mennat I. Mehrez ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Tooth Development ◽  
Gene Mutations ◽  
Cathepsin K ◽  
Autosomal Recessive Disorder ◽  
Novel Mutations ◽  
Raising Awareness ◽  
Egyptian Patients ◽  
Molecular Evaluation

Pycnodysostosis is a rare autosomal recessive disorder with characteristic diagnostic manifestations. This study aims to phenotype and provide molecular characterization of Egyptian patients, with emphasis on identifying unusual phenotypes and raising awareness about pycnodysostosis with different presentations to avoid a mis- or under-diagnosis and consequent mismanagement. We report on 22 Egyptian pycnodysostosis patients, including 9 new participants, all descending from consanguineous families and their ages ranging from 6 to 15 years. In addition, prenatal diagnosis was performed in one family with affected siblings. They all presented with short stature, except for one patient who presented with pancytopenia as her primary complaint. Moreover, 41.2% of patients had sleep apnea, 14% presented with craniosynostosis, and 44.4% had failure of tooth development. Molecular analysis via direct exome sequencing of the cathepsin K gene revealed three novel mutations ((NM_000396.3) c.761_763delCCT, c.864_865delAA, and c.509G>T) as well as two previously reported mutations among nine new cases. The following is our conclusion: This study expands the molecular spectrum of pycnodysostosis by identifying three novel mutations and adds to the clinical and orodental aspects of the disease. The link between the CTSK gene mutations and the failure of tooth development has not been established, and further studies could help to improve our understanding of the molecular pathology.

Two new gene mutations for late onset mitochondrial neurogastrointestinal encephalopathy (MNGIE)

2012 ◽  
Vol 3 (4) ◽  
Author(s):  
Gathline Etienne ◽  
Khadijah Shamseddine ◽  
Michael Pulley ◽  
Fatima Milfred
Keyword(s):  
Peripheral Neuropathy ◽  
Autosomal Recessive ◽  
Late Onset ◽  
Gene Mutations ◽  
Autosomal Recessive Disorder ◽  
Progressive External Ophthalmoplegia ◽  
Novel Mutations ◽  
New Gene

AbstractMitochondrial neurogastrointestinal encephalopathy (MNGIE) is a multisystem, autosomal recessive disorder characterized by ptosis, progressive external ophthalmoplegia, gastroparesis cachexia, peripheral neuropathy, and diffuse leukoencephalopathy. MNGIE is rare and the prevalence is unknown, however, to date there have been 76 mutations reported in the TYMP gene associated with MNGIE. We report two novel mutations that have not been previously described in a patient with clinical MNGIE syndrome.

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 Prevalence of CYP17A1 gene mutations in 17α-hydroxylase deficiency in the Chinese Han population

2019 ◽  
Vol 25 (1) ◽  
Author(s):  
Menglin Wang ◽  
Hao Wang ◽  
Haiying Zhao ◽  
Ling Li ◽  
Min Liu ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Gene Mutations ◽  
Autosomal Recessive Disorder ◽  
Chinese Han ◽  
Hydroxylase Deficiency ◽  
Case Presentation ◽  
Chinese Populations ◽  
Pathogenic Variants ◽  
Cytochrome P450 Family ◽  
Chinese Girls

Abstract Background 17α-hydroxylase deficiency is a rare autosomal recessive disorder caused by mutations in the cytochrome P450 family 17 subfamily A member 1 gene. The major clinical presentation includes hypertension, hypokalemia, male pseudohermaphroditism and female gonadal dysplasia. Hundreds of pathogenic variants have been reported in this disorder, and some common mutations were found to be race-specific. Case presentation In this study, we reported 5 Chinese girls with 17α-hydroxylase deficiency from Henan Province. The patients all came to the hospital for hypertension, and they also presented with sexual infantilism. The average age of the patients was 14 years old, ranging from 12 to 17 years old. They all had reduced blood cortisol, estradiol (E2), and testosterone (TESTO) and increased adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). They all had the appearance of females; however, three of the chromosome karyotypes were 46XX, and two were 46XY. Conclusions All of the patients carried a mutation on the 329 amino acid of CYP17A1 exon 6. By summarizing the currently known pathogenic mutations of 17α-hydroxylase deficiency, we demonstrated the prevalence of these gene mutations in Chinese Han and non-Chinese populations.

scholarly journals In Silico Analysis of B3GALTL Gene Reveling 13 Novel Mutations Associated with Peters’-plus syndrome

2020 ◽  
Author(s):  
Abdelrahman H. Abdelmoneim ◽  
Arwa A. Satti ◽  
Miysaa I. Abdelmageed ◽  
Naseem S. Murshed ◽  
Nafisa M. Elfadol ◽  
...  
Keyword(s):  
In Silico ◽  
Autosomal Recessive ◽  
In Silico Analysis ◽  
Autosomal Recessive Disorder ◽  
Coding Region ◽  
Novel Mutations ◽  
Physiochemical Properties ◽  
Peters Anomaly ◽  
Systemic Manifestations ◽  
Silico Analysis

AbstractBackgroundPeters’-plus syndrome is a rare autosomal recessive disorder, which is characterized by a specific malformation of the eye that includes corneal opaqueness and iridocorneal adhesions (Peters’ anomaly) along with other systemic manifestations. Furthermore, various researches report the association between B3GALTL gene and Peters’-plus syndrome. In the current work we aim to analyze the deleterious SNPs in B3GALTL gene that predispose to Peters’-plus syndrome.Methodthe associated SNPs of the coding region of the B3GALTL gene was acquired from National Center for Biotechnology Information and then analyzed by eight softwares (SIFT, Polyphen2, Proven, SNAP2, SNP@GO, PMut, Imutant and Mupro). The physiochemical properties of the resulted SNPs were then analyzed by Hope project website and visualized by chimera software.ResultThirteen novel mutations (Y172C, A222V, C260R, C260Y, D349G, I354K, R377C, G379C, G393R, G393E, G395E, G425E, R445W) are discovered in B3GALTL gene to cause deleterious effects leading to the development of Peters’-plus syndrome.ConclusionThirteen novel mutations in B3GALTL gene are predicted to cause Peters’-plus syndrome.

scholarly journals Case Report: Diabetes in Chinese Bloom Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Mingqun Deng ◽  
Miao Yu ◽  
Ruizhi Jiajue ◽  
Kai Feng ◽  
Xinhua Xiao
Keyword(s):  
Case Report ◽  
Chinese Population ◽  
Autosomal Recessive ◽  
Molecular Mechanisms ◽  
Autosomal Recessive Disorder ◽  
Bloom Syndrome ◽  
Clinical Spectrum ◽  
Sequence Variant ◽  
First Case ◽  
Helicase Gene

Bloom syndrome (BS) is a rare autosomal recessive disorder that causes several endocrine abnormalities. So far, only one BS pedigree, without diabetes, has been reported in the Chinese population. We presented the first case of BS with diabetes in the Chinese population and explored the clinical spectrum associated with endocrine. Possible molecular mechanisms were also investigated. Our study indicated that BS may be one rare cause of diabetes in the Chinese population. We also found a new pathogenic sequence variant in BLM (BLM RecQ like helicase gene)(NM_000057.4) c.692T>G, which may expand the spectrum of BLM variants.

Novel mutations in the SLC25A13 gene in a patient with NICCD and severe manifestations

2015 ◽  
Vol 28 (3-4) ◽  
Author(s):  
Hong Wang ◽  
Sainan Shu ◽  
Chen Chen ◽  
Zhihua Huang ◽  
DaoWen Wang
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Novel Mutations ◽  
Citrin Deficiency

AbstractNeonatal intrahepatic cholestatic due to citrin deficiency (NICCD) is an autosomal recessive disorder caused by mutations in the

scholarly journals Alpha 1 antitrypsin deficiency: a rare allele in patients from south of Italy

2019 ◽  
Vol 6 (2) ◽  
pp. 32-35
Author(s):  
Maddaloni V ◽  
Pepe N ◽  
Morano F ◽  
Lanzo M ◽  
Darco D ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Autosomal Recessive ◽  
Mutational Analysis ◽  
Gene Mutations ◽  
Autosomal Recessive Disorder ◽  
Rare Allele ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Plasma Glycoprotein ◽  
Alpha 1 Antitrypsin

Congenital α1-antitrypsin deficiency (AATD) is an autosomal recessive disorder, in Italy it is estimated that 1 in 5000 individuals may suffer from severe AATD. The AATD pathogenesis is directly related to gene mutations, which are highly polymorphic: in fact, more than 120 genetic variants closely associated with specific plasma glycoprotein concentrations have been identified. All the variants have a different clinical significance as they can cause an increase of occurrence of some pathologies such as emphysema, acute or chronic liver disease, cirrhosis, or liver failure. In particular, emphysema affects 54% of patients diagnosed with this deficit. The purpose of our study was to perform a mutational analysis of the AAT gene in order to highlight a genotype-serum correlation of AAT: we found subjects heterozygous for the rare allele PiMProcida and correlated its presence with a marked lowering of serum AAT levels.

scholarly journals Mutation spectrum and biochemical features in infants with neonatal Dubin-Johnson syndrome

2020 ◽  
Author(s):  
Kwang Yeon Kim ◽  
Tae Hyeong Kim ◽  
Moon-Woo Seong ◽  
Sung Sup Park ◽  
Jin Soo Moon ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Genetic Mutation ◽  
University Hospital ◽  
Neonatal Cholestasis ◽  
Johnson Syndrome ◽  
Novel Variants ◽  
National University ◽  
Seoul National University

Abstract Background: Dubin-Johnson syndrome (DJS) is an autosomal recessive disorder presenting as isolated direct hyperbilirubinemia.DJS is rarely diagnosed in the neonatal period. The purpose of this study was to clarify the clinical features of neonatal DJS and to analyze the genetic mutation of adenosine triphosphate-binding cassette subfamily C member 2 (ABCC2).Methods: From 2013 to 2018, 135 infants with neonatal cholestasis at Seoul National University Hospital were enrolled. Genetic analysis was performed by neonatal cholestasis gene panel. To clarify the characteristics of neonatal DJS, the clinical and laboratory results of 6 DJS infants and 129 infants with neonatal cholestasis from other causes were compared.Results: A total of 8 different ABCC2 variants were identified among the 12 alleles of DJS. The most common variant was p.Arg768Trp (33.4%), followed by p.Arg100Ter (16.8%). Three novel variants were identified (p.Gly693Glu, p.Thr394Arg, and p.Asn718Ser). Aspartate transaminase (AST) and alanine transaminase (ALT) levels were significantly lower in infants with DJS than in infants with neonatal cholestasis from other causes. Direct bilirubin and total bilirubin were significantly higher in the infants with DJS.Conclusions: We found three novel variants in 6 Korean infants with DJS. When AST and ALT levels are normal in infants with neonatal cholestasis, genetic analysis of ABCC2 permits an accurate diagnosis.

scholarly journals Mutation spectrum and biochemical features in infants with neonatal Dubin-Johnson syndrome

2020 ◽  
Author(s):  
Kwang Yeon Kim ◽  
Tae Hyeong Kim ◽  
Moon-Woo Seong ◽  
Sung Sup Park ◽  
Jin Soo Moon ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Genetic Mutation ◽  
University Hospital ◽  
Neonatal Cholestasis ◽  
Johnson Syndrome ◽  
Novel Variants ◽  
National University ◽  
Seoul National University

Abstract Background: Dubin-Johnson syndrome (DJS) is an autosomal recessive disorder presenting as isolated direct hyperbilirubinemia.DJS is rarely diagnosed in the neonatal period. The purpose of this study was to clarify the clinical features of neonatal DJS and to analyze the genetic mutation of adenosine triphosphate-binding cassette subfamily C member 2 (ABCC2).Methods: From 2013 to 2018, 135 infants with neonatal cholestasis at Seoul National University Hospital were enrolled. Genetic analysis was performed by neonatal cholestasis gene panel. To clarify the characteristics of neonatal DJS, the clinical and laboratory results of 6 DJS infants and 129 infants with neonatal cholestasis from other causes were compared.Results: A total of 8 different ABCC2 variants were identified among the 12 alleles of DJS. The most common variant was p.Arg768Trp (33.4%), followed by p.Arg100Ter (16.8%). Three novel variants were identified (p.Gly693Glu, p.Thr394Arg, and p.Asn718Ser). Aspartate transaminase (AST) and alanine transaminase (ALT) levels were significantly lower in infants with DJS than in infants with neonatal cholestasis from other causes. Direct bilirubin and total bilirubin were significantly higher in the infants with DJS.Conclusions: We found three novel variants in 6 Korean infants with DJS. When AST and ALT levels are normal in infants with neonatal cholestasis, genetic analysis of ABCC2 permits an accurate diagnosis.

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