scholarly journals A Novel Mutation in the CLDN16 Gene in a Palestinian Family with Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis

2017 ◽  
Vol 07 (01) ◽  
pp. e32-e35
Author(s):  
Abdulsalam Abu-Libdeh ◽  
Bassam Abu-Libdeh ◽  
Ulla Abdulhag
Keyword(s):  
Renal Failure ◽  
Missense Mutation ◽  
Novel Mutation ◽  
Positive Family History ◽  
Male Infant ◽  
Molecular Testing ◽  
Loss Of Function ◽  
Renal Disorder ◽  
Exon 2 ◽  
Familial Hypomagnesemia

AbstractFamilial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive renal disorder characterized by excessive renal magnesium and calcium loss, bilateral nephrocalcinosis, and progressive renal failure, due to impaired tubular reabsorption in the thick ascending loop of Henle. FHHNC is caused by loss of function mutations in the claudin-16 gene (CLDN16) and claudin-19 gene (CLDN19). A 2-month-old male infant presented with convulsions during hypomagnesemia, hypocalcemia, and hypophosphatemia, biochemical findings were consistent with FHHNC. There is a positive family history of the death of a 12 years old sibling due to renal failure. Gene sequencing of the CLDN16 revealed a novel missense mutation with the replacement of T by C in codon 120 located in exon 2, predicting cysteine to arginine substitution p.Cys120Arg. This is the first description of this missense mutation and the first confirmation of FHHNC by molecular testing in a Palestinian family which enables genetic counseling and future prenatal diagnosis.

scholarly journals A Novel Mutation in the AVPR2 Gene in a Palestinian Family with Nephrogenic Diabetes Insipidus

2017 ◽  
Vol 07 (01) ◽  
pp. e1-e3
Author(s):  
Abdulsalam Abu-Libdeh ◽  
Isaiah Wexler ◽  
Imad Dweikat ◽  
David Zangen ◽  
Bassam Abu-Libdeh
Keyword(s):  
Diabetes Insipidus ◽  
Nephrogenic Diabetes Insipidus ◽  
Novel Mutation ◽  
Collecting Duct ◽  
Failure To Thrive ◽  
Male Infant ◽  
Gene Encoding ◽  
Exon 2 ◽  
Recessive Form ◽  
V2 Vasopressin Receptor

AbstractNephrogenic diabetes insipidus (NDI) is a urinary concentrating defect resulting from resistance of the collecting duct to the antidiuretic action of vasopressin (AVP). The X-linked recessive form is the most frequent genetic cause of inherited NDI and can be caused by mutations in the gene encoding the V2 vasopressin receptor (AVPR2). A Palestinian male infant presented in the neonatal period with failure to thrive, vomiting, irritability, fever, and polyuria, and had biochemical findings consistent with NDI. The diagnosis of NDI was established based on the clinical picture, absent response to desmopressin, and a similarly affected elder brother. Sequencing of the AVPR2 gene for the patient and his affected brother revealed a novel missense mutation with replacement of G by A in codon 82 located in exon 2 (TGC → TAC), causing a cysteine to tyrosine substitution (C82Y). Testing of the mother showed that she was the carrier of that mutation. This is the identified AVPR2 mutation in a Palestinian family. Knowledge of these mutations will allow genetic counseling and early diagnosis of affected males.

A Novel Mutation Glyl672→Arg in Type 2A and a Homozygous Mutation in Type 2B von Willebrand Disease

1996 ◽  
Vol 76 (02) ◽  
pp. 253-257 ◽  
Author(s):  
Takeshi Hagiwara ◽  
Hiroshi Inaba ◽  
Shinichi Yoshida ◽  
Keiko Nagaizumi ◽  
Morio Arai ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Novel Mutation ◽  
Point Mutations ◽  
Japanese Patients ◽  
Von Willebrand Disease ◽  
Homozygous Mutation ◽  
Missense Mutations ◽  
Reaction Products ◽  
Type 3 ◽  
Von Willebrand

SummaryGenetic materials from 16 unrelated Japanese patients with von Willebrand disease (vWD) were analyzed for mutations. Exon 28 of the von Willebrand factor (vWF) gene, where point mutations have been found most frequent, was screened by various restriction-enzyme analyses. Six patients were observed to have abnormal restriction patterns. By sequence analyses of the polymerase chain-reaction products, we identified a homozygous R1308C missense mutation in a patient with type 2B vWD; R1597W, R1597Q, G1609R and G1672R missense mutations in five patients with type 2A; and a G1659ter nonsense mutation in a patient with type 3 vWD. The G1672R was a novel missense mutation of the carboxyl-terminal end of the A2 domain. In addition, we detected an A/C polymorphism at nucleotide 4915 with HaeIII. There was no particular linkage disequilibrium of the A/C polymorphism, either with the G/A polymorphism at nucleotide 4391 detected with Hphl or with the C/T at 4891 detected with BstEll.

scholarly journals Novel Variant in CLDN16: A Further Step in the Diagnosis of Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis—A Case Report

Uro ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 76-81
Author(s):  
Gopal Narang ◽  
Tim Shimon ◽  
Jonathan Moore ◽  
Megan Hager ◽  
Filippo Pinto e Vairo ◽  
...  
Keyword(s):  
Renal Failure ◽  
Clinical Manifestations ◽  
Tight Junction Proteins ◽  
Early Progression ◽  
Significant Burden ◽  
Novel Variant ◽  
Familial Hypomagnesemia ◽  
Calcium And Magnesium ◽  
Junction Proteins ◽  
Electrolyte Abnormalities

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare tubulopathy characterized by renal loss of calcium and magnesium leading to progressive renal failure. The disorder is caused by variants to the tight junction proteins claudin-16 and -19. While rare, this disorder causes a significant burden to patients based on its clinical manifestations of various electrolyte abnormalities, nephrocalcinosis, and early progression to renal failure. In this report we describe the diagnosis of a novel variant of CLDN16 which clinically presented with severe hypomagnesemia, hypocalcemia, nephrocalcinosis, and renal failure.

The use of glimepiride for the treatment of neonatal diabetes mellitus caused by a novel mutation of the ABCC8 gene

2020 ◽  
Vol 33 (12) ◽  
pp. 1605-1608
Author(s):  
Xiao Qin ◽  
Jingzi Zhong ◽  
Dan Lan
Keyword(s):  
Diabetes Mellitus ◽  
Novel Mutation ◽  
Male Infant ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Rare Form ◽  
Case Presentation ◽  
Abcc8 Gene

AbstractObjectivesNeonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes that is usually diagnosed in the first six months of life.Case presentationWe report on a male infant with neonatal diabetes who presented with diabetic ketoacidosis at two months and 16 days. A novel homozygous missense mutation (c.259T>G) was identified in the ABCC8 gene. In this case, insulin was replaced with glimepiride at a dosage of 0.49 mg/kg/day at five months, and this achieved metabolic control and satisfactory growth as observed at follow-up.ConclusionsThis report improves our understanding of the mutational spectrum of ABCC8, which is normally associated with NDM, and shows that the treatment regimen for this condition can be successfully switched from insulin therapy to the use of sulfonylurea.

scholarly journals A Novel Mutation of ATP7B Gene in a Case of Wilson Disease

Medicina ◽  
2021 ◽  
Vol 57 (2) ◽  
pp. 123
Author(s):  
Cigdem Yuce Kahraman ◽  
Ali Islek ◽  
Abdulgani Tatar ◽  
Özlem Özdemir ◽  
Adil Mardinglu ◽  
...  
Keyword(s):  
Wilson Disease ◽  
Novel Mutation ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis ◽  
Compound Heterozygous ◽  
Atp7b Gene ◽  
Loss Of Function ◽  
Clinical Presentations ◽  
The Family ◽  
The Brain

Wilson disease (WD) (OMIM# 277900) is an autosomal recessive inherited disorder characterized by excess copper (Cu) storage in different human tissues, such as the brain, liver, and the corneas of the eyes. It is a rare disorder that occurs in approximately 1 in 30,000 individuals. The clinical presentations of WD are highly varied, primarily consisting of hepatic and neurological conditions. WD is caused by homozygous or compound heterozygous mutations in the ATP7B gene. The diagnosis of the disease is complicated because of its heterogeneous phenotypes. The molecular genetic analysis encourages early diagnosis, treatment, and the opportunity to screen individuals at risk in the family. In this paper, we reported a case with a novel, hotspot-located mutation in WD. We have suggested that this mutation in the ATP7B gene might contribute to liver findings, progressing to liver failure with a loss of function effect. Besides this, if patients have liver symptoms in childhood and/or are children of consanguineous parents, WD should be considered during the evaluation of the patients.

scholarly journals Clinical, Genetics, and Bioinformatic Characterization of Mutations Affecting an Essential Region of PLS3 in Patients with BMND18

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Ting Chen ◽  
Haiying Wu ◽  
Chenxi Zhang ◽  
Jiarong Feng ◽  
Linqi Chen ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Homology Modelling ◽  
Gene Sequencing ◽  
Bioinformatic Analysis ◽  
Actin Binding ◽  
Clinical Genetics ◽  
Loss Of Function ◽  
Mineral Density ◽  
Trait Locus ◽  
The Impact

Background. Bone mineral density quantitative trait locus 18 (BMND18, OMIM #300910) is a type of early-onset osteogenesis imperfecta (OI) caused by loss-of-function mutations in the PLS3 gene, which encodes plastin-3, a key protein in the formation of actin bundles throughout the cytoskeleton. Here, we report a patient with PLS3 mutation caused BMND18 and evaluated all the reported disease-causing mutations by bioinformatic analysis. Methods. Targeted gene sequencing was performed to find the disease-causing mutation in our patient. Bioinformatic analyses mainly including homology modelling and molecular dynamics stimulation were conducted to explore the impact of the previously reported mutations on plastin-3. Results. Gene sequencing showed a novel nonsense mutation (c.745G > T, p.E249X), which locates at a highly conserved region containing residues p.240–266 (LOOP-1) in the PLS3 gene. Further bioinformatic analyses of the previously reported mutations revealed that LOOP-1 is predicted to physically connect the calponin-homology 1 (CH1) and CH2 domains of the ABD1 fragment and spatially locates within the interface of ABD1 and ABD2. It is crucial to the conformation transition and actin-binding function of plastin-3. Conclusions. This report identified a novel mutation that truncates the PLS3 gene. Moreover, bioinformatic analyses of the previous reported mutations in PLS3 gene lead us to find a critical LOOP-1 region of plastin-3 mutations at which may be detrimental to the integral conformation of plastin-3 and thus affect its binding to actin filament.

scholarly journals Goα Regulates Volatile Anesthetic Action in Caenorhabditis elegans

Genetics ◽  
2001 ◽  
Vol 158 (2) ◽  
pp. 643-655 ◽  
Author(s):  
Bruno van Swinderen ◽  
Laura B Metz ◽  
Laynie D Shebester ◽  
Jane E Mendel ◽  
Paul W Sternberg ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Novel Mutation ◽  
Volatile Anesthetic ◽  
Loss Of Function ◽  
Wild Type ◽  
Α Subunit ◽  
C Elegans ◽  
Missense Mutant ◽  
Anesthetic Action ◽  
Mutant Phenotypes

Abstract To identify genes controlling volatile anesthetic (VA) action, we have screened through existing Caenorhabditis elegans mutants and found that strains with a reduction in Go signaling are VA resistant. Loss-of-function mutants of the gene goa-1, which codes for the α-subunit of Go, have EC50s for the VA isoflurane of 1.7- to 2.4-fold that of wild type. Strains overexpressing egl-10, which codes for an RGS protein negatively regulating goa-1, are also isoflurane resistant. However, sensitivity to halothane, a structurally distinct VA, is differentially affected by Go pathway mutants. The RGS overexpressing strains, a goa-1 missense mutant found to carry a novel mutation near the GTP-binding domain, and eat-16(rf) mutants, which suppress goa-1(gf) mutations, are all halothane resistant; goa-1(null) mutants have wild-type sensitivities. Double mutant strains carrying mutations in both goa-1 and unc-64, which codes for a neuronal syntaxin previously found to regulate VA sensitivity, show that the syntaxin mutant phenotypes depend in part on goa-1 expression. Pharmacological assays using the cholinesterase inhibitor aldicarb suggest that VAs and GOA-1 similarly downregulate cholinergic neurotransmitter release in C. elegans. Thus, the mechanism of action of VAs in C. elegans is regulated by Goα, and presynaptic Goα-effectors are candidate VA molecular targets.

scholarly journals Biochemical Characterization of the GBA2 c.1780G>C Missense Mutation in Lymphoblastoid Cells from Patients with Spastic Ataxia

2018 ◽  
Vol 19 (10) ◽  
pp. 3099 ◽  
Author(s):  
Anna Malekkou ◽  
Maura Samarani ◽  
Anthi Drousiotou ◽  
Christina Votsi ◽  
Sandro Sonnino ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Autosomal Recessive ◽  
Biochemical Characterization ◽  
Fold Increase ◽  
Loss Of Function ◽  
Spastic Paraplegia ◽  
Spastic Ataxia ◽  
Autosomal Recessive Cerebellar Ataxia ◽  
Compensatory Effect

The GBA2 gene encodes the non-lysosomal glucosylceramidase (NLGase), an enzyme that catalyzes the conversion of glucosylceramide (GlcCer) to ceramide and glucose. Mutations in GBA2 have been associated with the development of neurological disorders such as autosomal recessive cerebellar ataxia, hereditary spastic paraplegia, and Marinesco-Sjogren-Like Syndrome. Our group has previously identified the GBA2 c.1780G>C [p.Asp594His] missense mutation, in a Cypriot consanguineous family with spastic ataxia. In this study, we carried out a biochemical characterization of lymphoblastoid cell lines (LCLs) derived from three patients of this family. We found that the mutation strongly reduce NLGase activity both intracellularly and at the plasma membrane level. Additionally, we observed a two-fold increase of GlcCer content in LCLs derived from patients compared to controls, with the C16 lipid being the most abundant GlcCer species. Moreover, we showed that there is an apparent compensatory effect between NLGase and the lysosomal glucosylceramidase (GCase), since we found that the activity of GCase was three-fold higher in LCLs derived from patients compared to controls. We conclude that the c.1780G>C mutation results in NLGase loss of function with abolishment of the enzymatic activity and accumulation of GlcCer accompanied by a compensatory increase in GCase.

Jimpy-4J Mouse Has a Missense Mutation in Exon 2 of the Plp Gene

1997 ◽  
Vol 19 (4) ◽  
pp. 337-341 ◽  
Author(s):  
Gail B. Pearsall ◽  
Nancy L. Nadon ◽  
Merrill K. Wolf ◽  
Susan Billings-Gagliardi
Keyword(s):  
Missense Mutation ◽  
Exon 2 ◽  
I Gene

scholarly journals Bilateral Renal Tumour as Indicator for Birt-Hogg-Dubé Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
P. C. Johannesma ◽  
R. J. A. van Moorselaar ◽  
S. Horenblas ◽  
L. E. van der Kolk ◽  
E. Thunnissen ◽  
...  
Keyword(s):  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Positive Family History ◽  
Renal Tumour ◽  
Molecular Testing ◽  
Familial History ◽  
Lung Cysts ◽  
History Of ◽  
Bhd Syndrome

Birt-Hogg-Dubé (BHD) syndrome is a cancer disorder caused by a pathogenicFLCNmutation characterized by fibrofolliculomas, lung cysts, pneumothorax, benign renal cyst, and renal cell carcinoma (RCC). In this case we describe a patient with bilateral renal tumour and a positive familial history for pneumothorax and renal cancer. Based on this clinical presentation, the patient was suspected for BHD syndrome, which was confirmed after molecular testing. We discuss the importance of recognizing this autosomal dominant cancer disorder when a patient is presented at the urologist with a positive family history of chromophobe renal cell cancer or a positive familial history for renal cell cancer and pneumothorax.

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