Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identification of p.Arg205Cys in CASR in an autosomal dominant hypocalcaemia type 1 pedigree: A case report.

ABSTRACT:

Rationale

Autosomal dominant hypocalcaemia type 1 (ADH1) is a genetic disease characterized by benign hypocalcemia, inappropriately low parathyroid hormone levels and mostly hypercalciuria. It is caused by the activating mutations of the calcium-sensing receptor gene (CASR), which produces a left-shift in the set point for extracellular calcium.

Patient concerns

A 50-year-old man presenting with muscle spasms was admitted into the hospital. He has a positive familial history for hypocalcemia. Auxiliary examinations demonstrated hypocalcemia, hyperphosphatemia, normal parathyroid hormone level and nephrolithiasis. A missense heterozygous variant in CASR, c 613C > T (p. Arg205Cys) which has been reported in a familial hypocalciuric hypercalcemia type 1 patient was found in the patient's genotype. It is the first time that this variant is found associating with ADH1. The variant is predicted vicious by softwares and cosegregates with ADH1 in this pedigree. CASR Arg205Cys was deduced to be the genetic cause of ADH1 in the family.

Diagnosis

The patient was diagnosed with ADH1 clinically and genetically.

Interventions

Oral calcitriol, calcium and hydrochlorothiazide were prescribed to the patient.

Outcomes

After the treatments for 1 week, the patient's symptom was improved and the re-examination revealed serum calcium in the normal range. A 3-month follow-up showed his symptom was mostly relieved.

Lessons

The variant of CASR Arg205Cys, responsible for ADH1 in this family, broadened the genetic spectrum of ADH1. Further and more studies are required to evaluate the correlation between genotype and phenotype in ADH1 patients.

SUBMITTER: Ji Y

PROVIDER: S-EPMC8238359 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

A Neonatal Case of Autosomal Dominant Hypoparathyroidism without Mutation of the CASR Gene.

Project description:We experienced a case of familial hypoparathyroidism with an autosomal dominant pattern of transmission and performed molecular analysis of the calcium-sensing receptor (CASR) gene. The patient was a female neonate, born by cesarean section at term because of breech presentation. Her mother had been diagnosed with idiopathic hypoparathyroidism at the age of 9 yr and had been receiving vitamin D treatment since then. At birth, the patient's serum calcium concentration was 8.4 mg/dl, but it fell to 4.0 mg/dl on the fifth day after birth. Furthermore, her serum intact PTH level was inappropriately low, while hyperphosphatemia and hypomagnesemia were found. She was diagnosed with familial hypoparathyroidism, and was immediately started on oral administration of 1?(OH)D3 (0.1 µg/kg/day) and continuous intravenous infusion of 8.5% calcium gluconate. Additionally, trichlormethiazide was administered because of elevated urinary calcium/creatinine (Ca/Cr) ratio. Her serum calcium concentration gradually improved thereafter. In this case, autosomal dominant hypocalcemia (ADH) due to abnormality in the CASR gene was clinically suspected, but DNA sequencing analysis revealed no mutation of the CASR gene in either the patient or her mother. This result suggests that the patient's hypoparathyroidism may have been caused by abnormality in a gene other than CASR.

| S-EPMC4004876 | biostudies-literature

Novel Mutation in the CASR Gene (p.Leu123Ser) in a Case of Autosomal Dominant Hypocalcemia.

Project description:Autosomal dominant hypocalcemia, caused by activating mutations of the calcium-sensing receptor (CASR) gene, is characterized by hypocalcemia with an inappropriately low concentration of parathyroid hormone (PTH). In this report, we describe the identification of a novel missense mutation in the CASR gene, in a boy with autosomal dominant hypocalcemia. Polymerase chain reaction (PCR)-single strand and DNA sequencing revealed a heterozygous mutation in CASR gene that causes a leucine substitution for serine at codon 123 (p.Leu123Ser). This mutation was absent in DNA from 50 control patients. In silico studies suggest that the identified variant was likely pathogenic. Sequencing analysis in the mother suggested mosaicism for the same variant, and she was clinically and biochemically unaffected. Clinical manifestations of the index case started with seizures at 14 months of age; cognitive impairment and several neuropsychological disabilities were noted during childhood. Extrapyramidal signs and basal ganglia calcification developed later, namely, hand tremor and rigidity at the age of 7 and 18 years, respectively. Laboratory analysis revealed hypocalcemia, hyperphosphatemia, and low-serum PTH with hypomagnesemia and mild hypercalciuria. After 2 years of treatment with calcium supplements and calcitriol, some brief periods of clinical improvement were reported; as well as an absence of nephrocalcinosis.

| S-EPMC4906418 | biostudies-literature

Autosomal dominant hypocalcemia with a novel <i>CASR</i> mutation: a case study and literature review.

Project description:Autosomal dominant hypocalcemia type 1 (ADH1) is a rare inherited disorder characterized by hypocalcemia with low parathyroid hormone (PTH) levels and high urinary calcium. Its clinical presentation varies from mild asymptomatic to severe hypocalcemia. It is caused by gain-of-function mutations in the calcium-sensing receptor gene (CASR) which affect PTH secretion from the parathyroid gland and calcium resorption in the kidney. Here, we describe a case who presented with symptoms of recurrent seizure caused by hypocalcemia with a novel CASR variant. We comprehensively analyzed the phenotypic features of this presentation and reviewed the current literature to better understand clinical manifestations and the genetic spectrum.

| S-EPMC9280832 | biostudies-literature

GATAD2B Gene Microdeletion Causing Intellectual Disability Autosomal Dominant Type 18: Case Report and Review of the Literature.

Project description:Pathogenic variants of the GATAD2B gene (1q21.3) are linked to intellectual disability autosomal dominant type 18 (MRD18; MIM 615074), characterized by dysmorphic features, psychomotor and language delay. We present an 11-year-old female patient with intellectual disability and typical clinical characteristics of MRD18. Chromosomal microarray analysis (CMA) revealed a novel CNV, approximately 200 kb in size and showed that the INTS3 and SLC27A3 genes are completely deleted along with the first 10 exons of the GATAD2B gene. INTS3 encodes the integrator complex subunit 3 and is part of the complex that maintains genome stability; SLC27A3 encodes a fatty acid transporter and has been associated with autism spectrum disorder. GATAD2B haploinsufficiency is associated with the phenotype. Furthermore, the girl had other clinical characteristics not previously described, such as emotional instability, calf hypotrophy, hypoplastic digit pads, tapered thumbs, and anterior earlobe crease. This study highlights the importance of the phenotype-genotype correlation using molecular diagnostic techniques, such as CMA, and its impact on precise diagnosis, treatment, prognosis, and genetic counseling for patients and their families.

| S-EPMC6738330 | biostudies-literature

Autosomal Dominant Hypophosphatemic Rickets: A Case Report and Review of the Literature.

Project description:Autosomal dominant hypophosphatemic rickets (ADHR) is an extremely rare form of genetic rickets caused by mutations in the fibroblast growth factor 23 gene. ADHR is characterized by hypophosphatemia secondary to isolated renal phosphate wasting. Only a few cases of ADHR have been reported in the literature to date. We describe the case of a 17-month-old girl who presented with severe failure to thrive (length: -4.08 standard deviation (SD), weight: -2.2 SD) and hypotonia. Hypophosphatemia, decreased tubular phosphate reabsorption (69%), and rachitic lesions were found. Genetic analysis showed the heterozygous variant c.536G>A (NM_020638.3:c.536G>A) in exon 3 of the FGF23 gene, leading to the diagnosis of ADHR. She was treated with phosphate salts and oral alfacalcidol. After 4 years of treatment, at 5 years of age, the patient's ADHR resolved spontaneously. Considering the lack of knowledge regarding ADHR, we reviewed the literature to describe the features of this rare and poorly understood disease. Eleven ADHR pediatric cases have been described thus far, with cases tending to be more common in females than males. Similar to the general population, two groups of patients with ADHR can be described depending on the mutations present: patients with an R179 and R176 mutation have early-onset of disease and higher frequency of rickets, and a milder and late-onset of disease, respectively. Symptoms and disease severity may fluctuate. Spontaneous remission may occur during the pediatric age.

| S-EPMC8392413 | biostudies-literature

LRP5 high bone mass (Worth-type autosomal dominant endosteal hyperostosis): case report and historical review of the literature.

Project description:PurposeLRP5 high bone mass (HBM) is an autosomal dominant endosteal hyperostosis caused by mutations of the low-density lipoprotein receptor-related protein 5 (LRP5) gene. Alternative names included "autosomal dominant osteosclerosis" and "Worth disease." The aim of the paper is to provide an historical overview of a disorder whose literature is complicated and confusing due to the past use of several denominations and lack of reviews.MethodsWe collected case reports of HBM with evidence of autosomal dominant transmission preceding the identification of the LRP5 mutations in 2002 (Worth-type endosteal hyperostosis) and cases of LRP5 HBM confirmed by genetic analysis since 2002. The prevalence of relevant clinical and laboratory findings was estimated. We described an affected woman with neurological manifestations.ResultsA 44-year-old Caucasian woman with torus palatinus complained of headache, hypo-/anosmia, and complete mixed deafness. Dual-energy X-ray absorptiometry (DEXA) scan revealed elevated bone mass. The A242T mutation of the LRP5 gene was detected. Including the present case, 155 patients have been reported to date. Neurological involvement and increased serum alkaline phosphatase (ALP) were present in 19.4% and 3.7% of cases, respectively. Facial changes and torus palatinus were observed in 61% and 41% of cases, respectively.ConclusionsWe present the only historical review on Worth-type endosteal hyperostosis, now known as LRP5 HBM. Neurological manifestations, previously considered absent in the disease, affect 19.4% of the patients. Genetic analysis and appropriate denomination of LRP5 HBM are fundamental for diagnosis and to mitigate the confusion that has long characterized this disease.

| S-EPMC10474981 | biostudies-literature

Autosomal dominant polycystic kidney disease and minimal trauma: medical review and case report.

Project description:BackgroundBlunt abdominal trauma in the setting of polycystic kidney disease is still scantly described in the literature and management guidelines of such patients are not well-established.Case presentationThe authors herein present a case of hypovolemic shock secondary to segmental renal artery bleed in a 75-year-old man with polycystic kidney disease after minimal blunt abdominal trauma, who underwent successful selective arterial embolization, and provide a thorough review of similar cases in the literature, while shedding the light on important considerations when dealing with such patients.ConclusionsIt is important to suspect renal injury in patients with pre-existing renal lesions irrespective of the mechanism of injury; and, vice-versa to suspect an underlying abnormality in patients with a clinical deterioration that's out of proportion to the mechanism of injury.

| S-EPMC6211544 | biostudies-literature

Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

Project description:We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease.

| S-EPMC6898984 | biostudies-literature

Whole-exome sequencing identifies a de novo PDE3A variant causing autosomal dominant hypertension with brachydactyly type E syndrome: a case report.

Project description:BACKGROUND:Autosomal dominant hypertension with brachydactyly type E syndrome caused by pathogenic variants in the PDE3A gene was first reported in 2015. To date, there are only a few reports of this kind of syndrome. Other patients still lack a genetic diagnosis. CASE PRESENTATION:Whole-exome sequencing was performed in an 18-year-old female proband with a clinical diagnosis of hypertension with brachydactyly syndrome. Quantitative real-time PCR was used to identify pathogenic copy number variations (CNVs). After bioinformatics analysis and healthy control database filtering, we revealed a heterozygous missense PDE3A variant (c.1346G?>?A, p.Gly449Asp). The variant was absent in the ExAC database and located in a highly evolutionarily conserved cluster of reported PDE3A pathogenic variants. Importantly, this variant was predicted to affect protein function by both SIFT (score?=?0) and PolyPhen-2 (score?=?1). After Sanger sequencing, the variant was determined to be absent in the healthy parents of the proband as well as 800 ethnically and geographically matched healthy controls. CONCLUSION:We present a report linking a de novo PDE3A variant to autosomal dominant hypertension with brachydactyly type E syndrome.

| S-EPMC7336660 | biostudies-literature

A RARE CASE OF ACROMEGALY AND AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE: CASE REPORT AND BRIEF REVIEW OF LITERATURE.

Project description:Objective:Acromegaly is a classic endocrine disorder caused by a growth hormone (GH)-secreting pituitary adenoma in an overwhelming majority of patients. The diagnosis may be delayed by several years due to the slow growing and insidious nature of the disease. Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by multiple renal cysts and various other systemic manifestations. The purpose of this article is to report a rare case of acromegaly with coexistent ADPKD. Methods:We report a case of 42-year-old female with acromegaly and ADPKD along with a brief review of literature. Results:The patient was referred to us for evaluation of progressive acral enlargement and coarsening of facial features. Endocrine evaluation confirmed the diagnosis of acromegaly due to an underlying GH-secreting pituitary macroadenoma. She was also found to have ADPKD. We discuss the clinical features and management of the patient. Conclusion:The association of pituitary adenomas and ADPKD is very rare and interesting. All affected individuals with pituitary adenomas and ADPKD in the literature are women. Furthermore, all reported pituitary adenomas in these individuals (including ours) are functional GH-secreting ones. These findings argue against a mere chance association between the two diseases.

| S-EPMC6876956 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data