Rare Cause of Infantile Hypercalcemia: A Novel Mutation in the SLC34A1 Gene

2018 ◽  
Vol 91 (4) ◽  
pp. 278-284 ◽  
Author(s):  
Erdal Kurnaz ◽  
Şenay Savaş Erdeve ◽  
Semra Çetinkaya ◽  
Zehra Aycan
Keyword(s):  
Metabolic Alkalosis ◽  
Novel Mutation ◽  
Gene Mutations ◽  
Phosphate Homeostasis ◽  
Clinical Syndromes ◽  
Wide Range ◽  
Medullary Nephrocalcinosis ◽  
Proximal Tubular ◽  
Idiopathic Infantile Hypercalcemia ◽  
Sodium Replacement

Background: Under physiological conditions, proximal tubular phosphate reabsorption via NaPi-IIa (and NaPi-IIc) ensures the maintenance of phosphate homeostasis. Impairment of NaPi-IIa, encoded by SLC34A1, is associated with various overlapping clinical syndromes, including hypophosphatemic nephrolithiasis with osteoporosis, renal Fanconi’s syndrome with chronic kidney disease, and idiopathic infantile hypercalcemia and nephrocalcinosis. Methods: A patient was referred to our hospital due to hyponatremia, hyperkalemia, and hypophosphatemia, as well as persistent hypercalcemia after fluid therapy and sodium replacement. At admission to our hospital, potassium and sodium values were normal. After initiation of phosphorus therapy, hypokalemia and metabolic alkalosis were observed. Renal sonography showed bilateral medullary nephrocalcinosis. Analyses of the SLC34A1 gene were performed due to hypercalcemia and hypophosphatemia. Results: Gene analyses identified a novel homozygous c.682T>C (p.W228R) (p.Trp228Arg) mutation. There are no previous reports of patients with SLC34A1 gene mutations presenting with hypokalemia and metabolic alkalosis. Conclusion: Herein, we present a case of infantile hypercalcemia 2 with a very different phenotype from that of previously described patients. Our findings provide further evidence for the wide range of phenotypic heterogeneity associated with NaPi-IIa impairment.

Novel SLC12A3 mutation in Gitelman syndrome

2021 ◽  
Vol 14 (1) ◽  
pp. e238097
Author(s):  
Rita Veríssimo ◽  
Luís Leite de Sousa ◽  
Tiago J Carvalho ◽  
Pedro Fidalgo
Keyword(s):  
Metabolic Alkalosis ◽  
Autosomal Recessive ◽  
Novel Mutation ◽  
Gene Mutations ◽  
Urinary Calcium ◽  
Gitelman Syndrome ◽  
Renal Ultrasound ◽  
Calcium Excretion ◽  
Slc12a3 Gene ◽  
Specific Symptoms

Gitelman syndrome (GS) is an autosomal recessive disease characterised by the presence of hypokalaemic metabolic alkalosis with hypomagnesaemia and hypocalciuria. The prevalence of this disease is 1–10/40 000. GS is usually associated with mild and non-specific symptoms and many patients are only diagnosed in adulthood. The disease is caused by mutations in the SLC12A3 gene. We present the case of a 49-year-old man referred to a nephrology appointment due to persistent hypokalaemia and hypomagnesaemia. Complementary evaluation revealed hypokalaemia, hypomagnesaemia, metabolic alkalosis, hyperreninaemia, increased chloride and sodium urinary excretion, and reduced urinary calcium excretion. Renal function, remainder serum and urinary ionogram, and renal ultrasound were normal. A diagnosis of GS was established and confirmed with genetic testing which revealed a novel mutation in SLC12A3 (c.1072del, p.(Ala358Profs*12)). This novel mutation extends the spectrum of known SLC12A3 gene mutations and further supports the allelic heterogeneity of GS.

A Novel Mutation in NIPBL Gene with the Cornelia de Lange Syndrome and a 10q11.22-q11.23 Microdeletion in the Same Individual

2020 ◽  
Author(s):  
Haydar Bağış ◽  
Özden Öztürk ◽  
Semih Bolu ◽  
Bayram Taşkın
Keyword(s):  
Novel Mutation ◽  
Genetic Disorder ◽  
Gene Mutations ◽  
The Other ◽  
Cornelia De Lange Syndrome ◽  
Other Hand ◽  
Wide Range ◽  
Cornelia De Lange

AbstractThe Cornelia de Lange syndrome (CdLS) is a genetic disorder characterized by multisystemic malformations. CdLS is due to mutations in one of the following genes: NIPBL, SMC1A, SMC3, RAD21, and HDAC8. On the other hand, 10q11.2 deletions cause a wide range of presentations in patients. Approximately 40 cases with variable deletions of 10q11.2 have been reported in literature. Some of the reported cases involve the coexistence of duplication or deletion affecting one copy of the chromosome. However, deletion of chromosome 10q11.22-q11.23 and CdLS syndrome caused by NIPBL gene mutations have not been reported previously. This report, therefore, is the first to report their coexistence together.

Idiopathic infantile hypercalcemia: mutations in SLC34A1 and CYP24A1 in two siblings and fathers

2020 ◽  
Vol 33 (10) ◽  
pp. 1353-1358
Author(s):  
Ayla Güven ◽  
Martin Konrad ◽  
Karl P. Schlingmann
Keyword(s):  
Vitamin D ◽  
Stop Codon ◽  
Gene Mutations ◽  
Splice Site Mutation ◽  
Heterozygous Mutation ◽  
High Dose ◽  
Loss Of Function ◽  
Site Mutation ◽  
Medullary Nephrocalcinosis ◽  
Idiopathic Infantile Hypercalcemia

AbstractObjectivesBoth CYP24A1 and SLC34A1 gene mutations are responsible for idiopathic infantile hypercalcemia, whereas loss-of-function mutations in CYP24A1 (25-OH-vitamin D-24-hydroxylase) lead to a defect in the inactivation of active 1.25(OH)2D; mutations in SLC34A1 encoding renal sodium phosphate cotransporter NaPi-IIa lead to primary renal phosphate wasting combined with an inappropriate activation of vitamin D. The presence of mutations in both genes has not been reported in the same patient until today.Case presentationHypercalcemia was incidentally detected when a 13-month-old boy was being examined for urinary tract infection. After 21 months, hypercalcemia was detected in his six-month-old sister. High dose of vitamin D was not given to both siblings. Both of them also had hypophosphatemia and decreased tubular phosphate reabsorption. Intensive hydration, furosemide and oral phosphorus treatment were given. Bilateral medullary nephrocalcinosis was detected in both siblings and their father. Serum Ca and P levels were within normal limits at follow-up in both siblings. Siblings and their parents all carry a homozygous stop codon mutation (p.R466*) in CYP24A1. Interestingly, both siblings and the father also have a heterozygous splice-site mutation (IVS6(+1)G>A) in SLC34A1. The father has nephrocalcinosis.ConclusionsA biallelic loss-of-function mutation in the CYP24A1 gene was identified as responsible for hypercalcemia, hypercalciuria and nephrocalcinosis. In addition, a heterozygous mutation in the SLC34A1 gene, although not being the main pathogenic factor, might contribute to the severe phenotype of both patients.

scholarly journals ABCD1 gene mutation in an Italian family with X-linkedadrenoleukodystrophy: case series

2021 ◽  
Vol 2021 ◽  
Author(s):  
Angelika Mohn ◽  
Nella Polidori ◽  
Chiara Aiello ◽  
Cristiano Rizzo ◽  
Cosimo Giannini ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Novel Mutation ◽  
Family Members ◽  
Case Series ◽  
Gene Mutations ◽  
Nutritional Intervention ◽  
Haematopoietic Stem Cell ◽  
List Type ◽  
Wide Range

Summary Adrenoleukodystrophy is a peroxisomal X-linked recessive disease caused by mutations in the ABCD1 gene, located on the X-chromosome (Xq28). Gene mutations in patient with adrenoleukodystrophy induce metabolic alterations characterized by impaired peroxisomal beta-oxidation and accumulation of very long chain fatty acid (VLCFA) in plasma and in all tissues. Although nutritional intervention associated with a various mixture of oil prevents the accumulation of VLCFA, to date no causal treatment is available. Therefore, haematopoietic stem cell transplantation (HSCT) and gene therapy are allowed only for very early stages of cerebral forms diagnosed during childhood.We reported a case series describing five family members affected by X-linked adrenoleukodystrophy caused by a novel mutation of the ABCD1 gene. Particularly, three brothers were affected while the sister and mother carried the mutation of the ABCD1 gene. In this family, the disease was diagnosed at different ages and with different clinical pictures highlighting the wide range of phenotypes related to this novel mutation. In addition, these characteristics stress the relevant role of early diagnosis to properly set a patient-based follow-up. Learning points We report a novel mutation in the ABCD1 gene documented in a family group associated to an X-ALD possible Addison only phenotype. All patients present just Addison disease but with different phenotypes despite the presence of the same mutations. Further follow-up is necessary to complete discuss the clinical development. The diagnosis of ALD needs to be included in the differential diagnosis in all patients with idiopathic PAI through accurate evaluation of VLCFA concentrations and genetic confirmation testing. Early diagnosis of neurological manifestation is important in order to refer timely to HSCT. Further follow-up of these family members is necessary to characterize the final phenotype associated with this new mutation.

scholarly journals New PAX2 Mutation Associated with Polycystic Kidney Disease: A Case Report

2021 ◽  
Vol 15 ◽  
pp. 117955652199235
Author(s):  
Jessica Maria Forero-Delgadillo ◽  
Vanessa Ochoa ◽  
Natalia Duque ◽  
Jaime Manuel Restrepo ◽  
Hernando Londoño ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Novel Mutation ◽  
Clinical Manifestations ◽  
Renal Cysts ◽  
Renal Dysplasia ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Incomplete Penetrance ◽  
Wide Range ◽  
Stage Renal Disease

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end stage renal disease in children. Diagnosis by genetic testing has proven challenging due to its genetic and phenotypic heterogeneity, as well as incomplete penetrance. We report a case on a 16-months old female with a history of renal cysts and a PAX2 mutation. Case presentation: The patient presented with a prenatal diagnosis of Potter sequence and a postnatal diagnosis of renal cysts. An ultrasound at 20 weeks gestation revealed right renal agenesis and possible left renal dysplasia. Post natal genetic analyses identified a novel mutation in PAX2. Conclusion: Cystic kidney disease is often underdiagnosed due to its variable expressivity and wide range of clinical manifestations; PAX2 genetic screening should be considered for all patients with CAKUT.

scholarly journals Novel compound heterozygous EYS variants may be associated with arRP in a large Chinese pedigree

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Chunli Wei ◽  
Ting Xiao ◽  
Jingliang Cheng ◽  
Jiewen Fu ◽  
Qi Zhou ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Gene Mutations ◽  
Chinese Family ◽  
Compound Heterozygous ◽  
Missense Mutations ◽  
The Novel ◽  
Pathogenic Variants ◽  
Pathogenic Genes ◽  
Compound Heterozygous Variants ◽  
Normal Controls

Abstract As a genetically heterogeneous ocular dystrophy, gene mutations with autosomal recessive retinitis pigmentosa (arRP) in patients have not been well described. We aimed to detect the disease-causing genes and variants in a Chinese arRP family. In the present study, a large Chinese pedigree consisting of 31 members including a proband and another two patients was recruited; clinical examinations were conducted; next-generation sequencing using a gene panel was used for identifying pathogenic genes, and Sanger sequencing was performed for verification of mutations. Novel compound heterozygous variants c.G2504A (p.C835Y) and c.G6557A (p.G2186E) for the EYS gene were identified, which co-segregated with the clinical RP phenotypes. Sequencing of 100 ethnically matched normal controls didn’t found these mutations in EYS. Therefore, our study identified pathogenic variants in EYS that may cause arRP in this Chinese family. This is the first study to reveal the novel mutation in the EYS gene (c.G2504A, p.C835Y), extending its mutation spectrum. Thus, the EYS c.G2504A (p.C835Y) and c.G6557A (p.G2186E) variants may be the disease-causing missense mutations for RP in this large arRP family. These findings should be helpful for molecular diagnosis, genetic counseling and clinical management of arRP disease.

scholarly journals A case of necrotizing fasciitis due to Klebsiella following local application of steroids

2016 ◽  
Vol 7 (6) ◽  
pp. 97-99 ◽  
Author(s):  
Suhaib Rehaman Abdul ◽  
Robin George
Keyword(s):  
Necrotizing Fasciitis ◽  
Local Application ◽  
Causative Organism ◽  
Site Infection ◽  
Human Beings ◽  
Medical Sciences ◽  
Abdominal Infection ◽  
Clinical Syndromes ◽  
Wide Range ◽  
Intravascular Devices

Klebsiella organisms are known to cause a wide range of clinical syndromes in human beings which include pneumonia, urinary tract infection, abdominal infection, surgical site infection, soft tissue infection and infection of intravascular devices. The incidence is higher among immunocompromised individuals and those with chronic debilitating diseases like diabetes, alcoholism etc. This case report is regarding an elderly diabetic male who developed necrotizing fasciitis of leg following local application of steroids. The causative organism was Klebsiella, which is an unusual pathogen.Asian Journal of Medical Sciences Vol.7(5) 2016 97-99

Atypical presentation of rapid-onset dystonia–parkinsonism in a toddler with a novel mutation in the ATP1A3 gene

2021 ◽  
Vol 14 (8) ◽  
pp. e244152
Author(s):  
Aishwarya Ganesh ◽  
Samyuktha Sivakumar ◽  
RanjithKumar Manokaran ◽  
Udayakumar Narasimhan
Keyword(s):  
Novel Mutation ◽  
Gene Mutations ◽  
Paediatric Population ◽  
Rapid Onset ◽  
Lower Limbs ◽  
Muscle Rigidity ◽  
Atypical Presentation ◽  
Genetic Sequencing ◽  
Atypical Presentations ◽  
Atp1a3 Gene

ATP1A3 gene mutations can result in a spectrum of diseases with diverse neurological manifestations. One such disorder linked to this mutation is rapid-onset dystonia–parkinsonism (RDP), which manifests as dystonia with features of parkinsonism, such as tremors, rigidity, muscle spasms, and bulbar symptoms. Affected patients are typically adolescents or young adults, with symptoms occurring in a rostrocaudal pattern. We report a unique case of a 2-year-old child with an early onset, atypical presentation of RDP. In addition to motor developmental delay, he presented with muscle rigidity and mild asymmetric dystonia of the limbs, with the lower limbs being more affected than the upper limbs. Genetic sequencing of the child revealed a novel heterozygous autosomal dominant mutation of ATP1A3 gene c.173A>G (p. Tyr58Cys). This report highlights that RDP can present with atypical presentations in the paediatric population and adds to existing medical literature on the clinical spectrum of ATP1A3 genetic channelopathy.

Adrenal Gland

PEDIATRICS ◽  
1950 ◽  
Vol 5 (4) ◽  
pp. 761-761
Keyword(s):  
Adrenal Gland ◽  
Clinical Syndromes ◽  
Wide Range

This volume is particularly timely in view of the upsurge in interest in the adrenal gland as a result of the discoveries of Hench and co-workers. It represents a huge task in bringing together a large part of this voluminous literature. The 34 chapters cover a wide range of subjects from the anatomy and chemistry of the gland to clinical syndromes associated with disturbances in function. A great deal of valuable information on the comparative function in different species is included.

scholarly journals Krüppel-like factor 3 inhibition by mutated lncRNA Reg1cp results in human high bone mass syndrome

2019 ◽  
Vol 216 (8) ◽  
pp. 1944-1964 ◽  
Author(s):  
Mi Yang ◽  
Qi Guo ◽  
Hui Peng ◽  
Yu-Zhong Xiao ◽  
Ye Xiao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cells ◽  
Bone Mass ◽  
Noncoding Rna ◽  
Natural Compound ◽  
Novel Mutation ◽  
Gene Mutations ◽  
High Bone Mass ◽  
High Bone ◽  
Chinese Subjects

High bone mass (HBM) is usually caused by gene mutations, and its mechanism remains unclear. In the present study, we identified a novel mutation in the long noncoding RNA Reg1cp that is associated with HBM. Subsequent analysis in 1,465 Chinese subjects revealed that heterozygous Reg1cp individuals had higher bone density compared with subjects with WT Reg1cp. Mutant Reg1cp increased the formation of the CD31hiEmcnhi endothelium in the bone marrow, which stimulated angiogenesis during osteogenesis. Mechanistically, mutant Reg1cp directly binds to Krüppel-like factor 3 (KLF3) to inhibit its activity. Mice depleted of Klf3 in endothelial cells showed a high abundance of CD31hiEmcnhi vessels and increased bone mass. Notably, we identified a natural compound, Ophiopogonin D, which functions as a KLF3 inhibitor. Administration of Ophiopogonin D increased the abundance of CD31hiEmcnhi vessels and bone formation. Our findings revealed a specific mutation in lncRNA Reg1cp that is involved in the pathogenesis of HBM and provides a new target to treat osteoporosis.

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