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.

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.

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 Characterization of a Putative Founder Mutation that Accounts for the High Incidence of Cystinosis in Brittany

2001 ◽  
Vol 12 (10) ◽  
pp. 2170-2174
Author(s):  
VASILIKI KALATZIS ◽  
STÉPHANIE CHERQUI ◽  
GENEVIÈVE JEAN ◽  
BÉATRICE CORDIER ◽  
PIERRE COCHAT ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Founder Mutation ◽  
Pcr Amplification ◽  
Splice Site Mutation ◽  
Autosomal Recessive Disorder ◽  
Site Mutation ◽  
Live Births ◽  
Reverse Transcription Pcr ◽  
High Incidence

Abstract. Cystinosis is an autosomal recessive disorder, characterized by an accumulation of intralysosomal cystine, with an incidence of 1 in 100,000 to 200,000 live births. A higher incidence of cystinosis, 1 in 26,000 live births, has been reported in the western French province of Brittany. PCR amplification and sequencing has identified a 27-bp deletion starting 3 bp before the end of exon 8 and continuing into intron 8, 898-900+24del27, which has only been detected in families from this region. Reverse transcription—PCR amplification of RNA from an affected individual has shown that this mutation is indeed a splice-site mutation and results in the production of aberrant transcripts. These transcripts are predicted to either severely truncate cystinosin or alter its topology, thus accounting for the severe phenotype of these individuals. The mutation 898-900+24del27 has been identified in 7 of 18 alleles studied. This mutation is likely to be a founder mutation and would account for the higher incidence of cystinosis in Brittany.1

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 RANK‐dependent autosomal recessive osteopetrosis: Characterization of five new cases with novel mutations

2012 ◽  
Vol 27 (2) ◽  
pp. 342-351 ◽  
Author(s):  
Alessandra Pangrazio ◽  
Barbara Cassani ◽  
Matteo M Guerrini ◽  
Julie C Crockett ◽  
Veronica Marrella ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Novel Mutations ◽  
Autosomal Recessive Osteopetrosis

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.

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 Characterization of six novel mutations in CYBA: the gene causing autosomal recessive chronic granulomatous disease

2008 ◽  
Vol 141 (6) ◽  
pp. 848-851 ◽  
Author(s):  
Shahram Teimourian ◽  
Elham Zomorodian ◽  
Mohsen Badalzadeh ◽  
AliReza Pouya ◽  
Caroline Kannengiesser ◽  
...  
Keyword(s):  
Chronic Granulomatous Disease ◽  
Autosomal Recessive ◽  
Granulomatous Disease ◽  
Novel Mutations

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 Apparent mineralocorticoid excess syndrome in a Brazilian boy caused by the homozygous missense mutation p.R186C in the HSD11B2 gene

2008 ◽  
Vol 52 (8) ◽  
pp. 1277-1281 ◽  
Author(s):  
Fernanda Borchers Coeli ◽  
Lúcio Fábio Caldas Ferraz ◽  
Sofia H. V. de Lemos-Marini ◽  
Sumara Zuanazi Pinto Rigatto ◽  
Vera Maria Santoro Belangero ◽  
...  
Keyword(s):  
Mineralocorticoid Receptor ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disorder ◽  
Homozygous Mutation ◽  
Molecular Studies ◽  
Apparent Mineralocorticoid Excess ◽  
Gene Maps ◽  
Apparent Mineralocorticoid Excess Syndrome

The apparent mineralocorticoid excess syndrome (AME) is a rare autosomal recessive disorder due to the deficiency of 11β-hydroxysteroid dehydrogenase type 2 enzyme (11beta-HSD2). The 11beta-HSD2 enzyme, encoded by HSD11B2 gene, metabolizes active cortisol in cortisone. Mutations on HSD11B2 gene affect the enzyme activity by leading to an excess of cortisol, which causes its inappropriate access to mineralocorticoid receptor. Therefore, cortisol will bind mineralocorticoid receptor. The human HSD11B2 gene maps to chromosome 16q22 and consists of five exons encoding a protein of 405 amino acids. We present here clinical and molecular studies on a Brazilian boy who was born pre-term after an oligodramnious pregnancy. He was diagnosed as having AME at the age of 26 months. His parents are second cousins. Molecular characterization of the HSD11B2 gene revealed the homozygous mutation p.R186C. The patient described here is the second case of HDS11B2 gene mutation reported in Brazilian patients with AME.

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