Five Novel Mutations in Cystinuria Genes SLC3A1 and SLC7A9

Five Novel Mutations in Cystinuria Genes SLC3A1 and SLC7A9Cystinuria is an autosomal recessive disorder that is characterized by impaired transport of cystine, lysine, ornithine and arginine in the proximal renal tubule and epithelial cells of the gastrointestinal tract. The transport of these amino acids is mediated by the rBAT/b0,+AT transporter, the subunits of which are encoded by the genes SLC3A1, located on chromosome 2p16.3-21, and SLC7A9, located on chromosome 19q12-13.1. Based on the urinary cystine excretion patterns of obligate heterozygotes, cystinuria is classified into type I (normal amino acid urinary pattern in heterozygotes) and non type I (a variable degree of urinary hyper excretion of cystine and dibasic amino acids in heterozygotes). On the basis of genetic aspects, cystinuria is classified into type A, is caused by mutations in both alleles of SLC3A1; type B, caused by mutations in both alleles of SLC7A9 and type AB, is caused by one mutation in SLC3A1 and one mutation in SLC7A9. Here we present two novel mutations in the SLC3A1 gene (C242R and L573X), which were found in patients from Serbia, and three in the SLC7A9 gene (G73R, V375I, 1048-1051 delACTC), found in patients from Serbia, Macedonia and Turkey, respectively.

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Cardiovascular involvement in alpha-n-acetyl neuraminidase deficiency syndromes (sialidosis type I and II)

Cardiology in the Young ◽

10.1017/s1047951120004953 ◽

2021 ◽

pp. 1-3

Author(s):

Priyanka Prasanna ◽

Chenni S. Sriram ◽

Sarah H. Rodriguez ◽

Utkarsh Kohli

Keyword(s):

Autosomal Recessive ◽

Ventricular Dysfunction ◽

Clinical Presentation ◽

Clinical Course ◽

Rare Condition ◽

Autosomal Recessive Disorder ◽

Left Ventricular ◽

Type I ◽

Neonatal Onset ◽

Cardiovascular Involvement

Abstract Sialidosis, a rare autosomal recessive disorder, is caused by a deficiency of NEU1 encoded enzyme alpha-N-acetyl neuraminidase. We report a premature male with neonatal-onset type II sialidosis which was associated with left ventricular dysfunction. The clinical presentation and subsequent progression which culminated in his untimely death at 16 months of age are succinctly described. Early-onset cardiovascular involvement as noted in this patient is not well characterised. The case report is supplemented by a comprehensive review of the determinants, characteristics, and the clinical course of cardiovascular involvement in this rare condition.

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Novel truncating and missense mutations of the KCC3 gene associated with Andermann syndrome

Neurology ◽

10.1212/01.wnl.0000204181.31175.8b ◽

2006 ◽

Vol 66 (7) ◽

pp. 1044-1048 ◽

Cited By ~ 34

Author(s):

G. Uyanik ◽

N. Elcioglu ◽

J. Penzien ◽

C. Gross ◽

Y. Yilmaz ◽

...

Keyword(s):

Missense Mutation ◽

Autosomal Recessive ◽

Sensory Neuropathy ◽

Variable Degree ◽

Missense Mutations ◽

Novel Mutations ◽

The Third ◽

Truncating Mutation ◽

Cerebral Mri ◽

Different Types

Background: Andermann syndrome (OMIM 218000) is an autosomal recessive motor-sensory neuropathy associated with developmental and neurodegenerative defects. The cerebral MRI reveals a variable degree of agenesis of the corpus callosum. Recently, truncating mutations of the KCC3 gene (also known as SLC12A6) have been associated with Andermann syndrome.Methods: The authors assessed clinically and genetically three isolated cases from Germany and Turkey with symptoms consistent with Andermann syndrome.Results: The authors detected four novel mutations within the KCC3 gene in their patients: two different truncating mutations in the first patient, a homozygous truncating mutation in the second, and a homozygous missense mutation in the third patient. In contrast to the classic phenotype of the Andermann syndrome linked to truncating KCC3 mutations the phenotype and the course of the disease linked to the missense mutation appeared to be different (i.e., showing additional features like diffuse and widespread white matter abnormalities).Conclusions: Not only truncating but also missense mutations of the KCC3 gene are associated with Andermann syndrome. Different types of KCC3 mutations may determine different clinical phenotypes.

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

10.1101/2020.03.21.000695 ◽

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.

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Molecular Basis of Antithrombin Type I Deficiency: The First Large In-frame Deletion and Two Novel Mutations in Exon 6

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648909 ◽

1994 ◽

Vol 72 (04) ◽

pp. 534-539 ◽

Cited By ~ 3

Author(s):

J Emmerich ◽

G Chadeuf ◽

M Alhenc-Gelas ◽

M Gouault-Heilman ◽

P Toulon ◽

...

Keyword(s):

Amino Acids ◽

Stop Codon ◽

Direct Sequencing ◽

Gene Mutations ◽

Repeat Sequence ◽

Type I ◽

Novel Mutations ◽

Flanking Sequences ◽

At Deficiency ◽

Exon 4

SummaryWe report three novel mutations accounting for cases of inherited type I antithrombin (AT) deficiency. Using the polymerase chain reaction (PCR) and direct sequencing of the coding sequences of the AT gene, we found one mutation in exon 4 and two in exon 6. A deletion of 105 bp causing an in-frame deletion of 35 amino acids between Tyr 240 and Gly 276 was found in exon 4. In a second kindred, deletion of two adenines in codon 412-413 introduced a frameshift and a stop codon at position 431. The last mutation was an insertion of ACCG in codon 387, generating a frameshift with a stop codon located at the normal position.The finding of a sequence repeat of nine residues located at the 5’and 3’ ends of the deleted fragment might explain the 105 bp deletion by slippage and mispairing at the replication fork during DNA synthesis. The second mutation is the fourth described within a region of six amino acids (between Phe 408 and Arg 413), which seems to be a cluster of mutations. In this case, the presence of a double repeat sequence - TTCCT and AACA - flanking this region could be particularly favorable for slipped mispairing.These results confirm that human gene mutations are not random events but are strongly influenced by DNA flanking sequences.

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

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2014-0278 ◽

2015 ◽

Vol 28 (3-4) ◽

Cited By ~ 3

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

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Lysine Malabsorption Syndrome: A New Type of Transport Defect

PEDIATRICS ◽

10.1542/peds.57.1.102 ◽

1976 ◽

Vol 57 (1) ◽

pp. 102-105

Author(s):

Kiyoshi Omura ◽

Nobuko Yamanaka ◽

Shinobu Higami ◽

Osamu Matsuoka ◽

Akie Fujimoto ◽

...

Keyword(s):

Amino Acids ◽

Renal Tubule ◽

Normal Values ◽

The Other ◽

Loading Test ◽

Normal Limits ◽

Normal Absorption ◽

Transport Defect ◽

New Type ◽

Dibasic Amino Acids

A 21-month-old girl with physical and mental retardation is described. She excreted an increased amount of lysine in urine but no excessive quantities of arginine, ornithine, or cystine. Serum level of lysine was found to be low but the levels of the other amino acids were within normal limits. The endogenous renal clearance rates of amino acids showed a marked high value of lysine and normal values of the other dibasic amino acids. Oral loading test of amino acids revealed an impaired absorption of lysine and normal absorption of arginine, ornithine, and cystine in the intestine. These results indicate a specific defect in transport of lysine in the intestine as well as in the renal tubule.

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Congenital Amegakaryocytic Thrombocytopenia: A Brief Review of the Literature

Clinical Medicine Insights Pathology ◽

10.4137/cpath.s4972 ◽

2010 ◽

Vol 3 ◽

pp. CPath.S4972 ◽

Cited By ~ 11

Author(s):

Fatma S. Al-Qahtani

Keyword(s):

Bone Marrow ◽

Autosomal Recessive ◽

Autosomal Recessive Disorder ◽

Primary Treatment ◽

Bleeding Complications ◽

Type I ◽

Cell Transplant ◽

Missense Mutations ◽

Severe Type ◽

Marrow Stem Cell

Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare inherited autosomal recessive disorder that presents with thrombocytopenia and absence of megakaryocytes. It presents with bleeding recognized on day 1 of life or at least within the first month. The cause for this disorder appears to be a mutation in the gene for the thrombopoeitin (TPO) receptor, c-Mpl, despite high levels of serum TPO. Patients with severe Type I-CAMT carry nonsense Mpl mutations which causes a complete loss of the TPO receptor whereas those with Type II CAMT carry missense mutations in the Mpl gene affecting the extracellular domain of the TPO receptor. Differential diagnosis for severe CAMT includes thrombocytopenia with absent radii (TAR) and Wiskott-Aldrich syndrome (WAS). The primary treatment for CAMT is bone marrow transplantation. Bone Marrow/Stem Cell Transplant (HSCT) is the only thing that ultimately cures this genetic disease. Newer modalities are on the way, such as TPO-mimetics for binding towards partially functioning c-Mpl receptors and gene therapy. Prognosis of CAMT patients is poor, because all develop in childhood a tri-linear marrow aplasia that is always fatal when untreated. Thirty percent of patients with CAMT die due to bleeding complications and 20% -due to HSCT if it has been done.

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

Genes ◽

10.3390/genes12101552 ◽

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.

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

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2018-0263 ◽

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.

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

Translational Neuroscience ◽

10.2478/s13380-012-0042-9 ◽

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.

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