Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A rare homozygous variant of MC2R gene identified in a Chinese family with familial glucocorticoid deficiency type 1: A case report.

ABSTRACT:

Background

Melanocortin-2 receptor (MC2R), a member of the G protein-coupled receptor family, is selectively activated by adrenocorticotropic hormone (ACTH). variants in MC2R are associated with family glucocorticoid deficiency 1 (FGD1).

Case presentation

We first reported a Chinese family with two affected siblings with a homozygotic variant of c.712C>T/p.H238Y in MC2R, presenting with skin hyperpigmentation, hyperbilirubinemia, and tall stature. These individuals showed novel clinical features, including congenital heart defects, not been found in other FGD1 patients.

Conclusions

We reported a Chinese family with affected siblings having a homozygotic variant of c.712C>T/p.H238Y in MC2R.Our report may expand the genetic and clinical spectrum of FGD1.

SUBMITTER: Liu S

PROVIDER: S-EPMC10003339 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A rare homozygous variant of <i>MC2R</i> gene identified in a Chinese family with familial glucocorticoid deficiency type 1: A case report.

Liu ShuPing S Zeng Ting T Luo Cheng C Peng DanXia D Xu Xuan X Liu Qin Q Wu Qiong Q Lu Qin Q Huang FuRong F

Frontiers in endocrinology 20230224

<h4>Background</h4>Melanocortin-2 receptor (<i>MC2R</i>), a member of the G protein-coupled receptor family, is selectively activated by adrenocorticotropic hormone (ACTH). variants in <i>MC2R</i> are associated with family glucocorticoid deficiency 1 (FGD1).<h4>Case presentation</h4>We first reported a Chinese family with two affected siblings with a homozygotic variant of c.712C>T/p.H238Y in <i>MC2R</i>, presenting with skin hyperpigmentation, hyperbilirubinemia, and tall stature. These indivi ...[more]

PMID: 36909322

Similar Datasets

A Novel Homozygous <i>MC2R</i> Variant Leading to Type-1 Familial Glucocorticoid Deficiency.

Project description:ContextType 1 familial glucocorticoid deficiency (FGD) (OMIM #607397) is a rare autosomal recessive disorder due to mutations in melanocortin-2-receptor (MC2R) gene encoding the G protein-coupled adrenocorticotropic (ACTH) transmembrane receptor.ObjectiveThe aim of the study is to describe 2 siblings born to a healthy consanguineous family presenting with clinical and biochemical features of FGD, harboring a novel homozygous MC2R variant.MethodsBoth patients are siblings born at term via normal delivery with normal birth weights. The first sibling presented with symptoms of hypoglycemia, repeated episodes of infections starting from 2 days of age. At 18 months of age, low serum cortisol was found, and he was started on hydrocortisone replacement therapy. The second sibling developed hypoglycemia on day 1 after birth, investigations revealed low serum sodium and cortisol levels and was also commenced on hydrocortisone treatment. Whole exome sequencing (WES) and in vitro functional studies on cell line transfected with wild-type and mutant plasmid clones were undertaken.ResultsWES revealed a novel homozygous missense mutation c.326T>A, p.Leu109Gln in the MC2R gene. In-silico prediction tools predicted the effect of this mutation to be deleterious. In vitro study using HEK293 cells transfected with MC2R wild-type and mutant clones showed a defect in protein expression and cAMP generation when stimulated with ACTH.ConclusionHomozygous semiconserved p.Leu109Gln mutation disrupts cAMP production and MC2R protein expression leading to ACTH resistance. This study provides additional evidence that this novel pathogenic variant in MC2R results in FGD phenotypes.

| S-EPMC9049112 | biostudies-literature

An atypical case of familial glucocorticoid deficiency without pigmentation caused by coexistent homozygous mutations in MC2R (T152K) and MC1R (R160W).

Project description:ContextFamilial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterized by isolated cortisol deficiency. Mutations in the gene encoding the ACTH receptor (MC2R) account for 25% of cases. One significant feature is generalized skin hyperpigmentation, which is thought to be due to elevated ACTH acting on the melanocortin 1 receptor (MC1R).ObjectiveThe aim of the study was to determine the cause of a nonhyperpigmented case of FGD.PatientsThe patient presented at 4 yr of age with hypoglycemia after prolonged fasting during a respiratory tract infection. She had further hypoglycemic attacks and was diagnosed with isolated glucocorticoid deficiency at 6 yr of age. Her parents were consanguineous, and she had two unaffected sisters. Her physical examination was normal, except that her height and weight were greater than the 97th centile for a sex- and age-matched reference population. Interestingly, she had no hyperpigmentation despite very high ACTH levels.ResultsNucleotide sequence analysis revealed homozygous mutations c.478C>T in MC1R and c.455C>A in MC2R leading to R160W and T152K changes in the amino acid sequences, respectively. The R160W MC1R change has previously been implicated in a red hair/pale skin phenotype, and MC2R -T152K is trafficking defective. Both parents and two unaffected sisters were heterozygous for the MC1R mutation; additionally, one unaffected sister was heterozygous for the MC2R mutation, and the other was wild-type.ConclusionWe report an unusual case of FGD without hyperpigmentation due to coexistent MC1R/MC2R mutations. This case is important because it demonstrates for the first time that the assumption that the action of ACTH on MC1R causes skin hyperpigmentation is correct.

| S-EPMC3396854 | biostudies-literature

Novel Melanocortin 2 Receptor Variant in a Chinese Infant With Familial Glucocorticoid Deficiency Type 1, Case Report and Review of Literature.

Project description:Familial glucocorticoid deficiency type 1 (FGD1) is an autosomal recessive disorder caused by mutations in the melanocortin 2 receptor (MC2R) gene, characterized by a low or undetectable serum cortisol level and a high adrenocorticotropic hormone (ACTH) level. Clinical manifestations include hypoglycemia, seizure, skin hyperpigmentation, hyperbilirubinemia, cholestasis, and a tall stature. Some dysmorphic features such as, a prominent forehead, hypertelorism, a broad nasal bridge, and small tapering fingers, have been reported. Children with FGD1 may have other isolated endocrine abnormalities. To date, no patient with FGD1 has been reported in mainland China. Here we report on a Chinese patient with FGD1 having a novel MC2R gene variant, a mild transverse palm crease, hypertelorism, and subtle/transient endocrine abnormalities relating to all three zones of the adrenal cortex and thyroid gland. We also reviewed cases with dysmorphic features or additional endocrine abnormalities.

| S-EPMC6563654 | biostudies-literature

Familial glucocorticoid deficiency type 2: a case report.

Project description:Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease resulting from resistance to the action of adrenocorticotropic hormone (ACTH) on the adrenal cortex, which leads to isolated glucocorticoid deficiency with normal mineralocorticoid secretion. It may present in infancy or early childhood with hyperpigmentation, failure to thrive, recurrent infections, hypoglycemic attacks and convulsions that may result in coma or death. Laboratory investigations reveal low cortisol and androgen levels with high ACTH associated with normal reninaldosterone axis. The disorder may be caused by mutations in the gene of ACTH receptor (MC2R), or mutations in the newly described melanocortin- 2 receptor accessory protein (MRAP) namely, FGD type 1 and FGD type 2, respectively. Twenty five percent of FGD cases are due to the mutations of the ACTH receptor, while FGD type 2 accounts for approximately 15-20% of FGD cases. Here, we report a six-month-old male infant, who presented with recurrent hypoglycemic convulsions. Serum hormone analysis showed low cortisol and androgen levels associated with a high ACTH concentration. No mutation was found in the NR0B1 and MC2R genes excluding congenital adrenal hypoplasia and FGD type 1. We found a homozygous deletion (c. 106+1delG) in intron 3 of MRAP gene. To our knowledge, this is the first Turkish patient reported with FGD type 2 due to a known MRAP mutation.

| S-EPMC3005676 | biostudies-literature

Familial Glucocorticoid Deficiency Presenting with Tonic-Clonic Seizure: A Case Report.

Project description:IntroductionFamilial glucocorticoid deficiency (FGD) is a rare cause of adrenal insufficiency in children. The condition can present with features of low cortisol and high adrenocorticotropic hormone (ACTH). Late diagnosis can be associated with high morbidity and high mortality rates.PatientThe presented case was a three-year-old Saudi girl who presented with dehydration and seizures as a complication of hypoglycemia. The initial examination and investigations revealed hyperpigmentation and normal arterial blood pressure. The lab investigation and genetic study revealed hypoglycemia, metabolic acidosis, low serum cortisol: 53 nmol/L (N: 140-690 nmol/L), normal androgens: 0.65 nmol/L (N: 0.5-2.4 nmol/L) and aldosterone: 50 pgmL (N: 2-200 pg/mol), and normal serum electrolytes. The ACTH level was more than 2000 pg/mL. A genetic study indicated a homozygous likely variant in the nicotinamide nucleotide transhydrogenase (NNT) gene, consistent with a genetic diagnosis of autosomal recessive glucocorticoid deficiency type 4. No mutations were found regarding MC2R, MRAP, and TXNRD2.Intervention and outcomeThe child was started on hydrocortisone, initially at 100 mg/m2/dose IV and then 100 mg/m2/day divided to q 6 hr. The dose was gradually decreased to 15 mg/m2/day PO BID, with clinical improvement and normalization of the serum ACTH level.ConclusionsThe autosomal recessive glucocorticoid deficiency, a variant of FGD type 4, is a very rare condition that may lead to high rates of mortality when the diagnosis and treatment occur late. Therefore, early diagnosis and treatment is essential for good outcomes.

| S-EPMC9955549 | biostudies-literature

Isolated Addison's disease is unlikely to be caused by mutations in MC2R, MRAP or STAR, three genes responsible for familial glucocorticoid deficiency.

Project description:BackgroundFamilial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease caused by ACTH resistance and leads to isolated glucocorticoid deficiency. Although FGD patients typically have normal mineralocorticoid secretion, subtle alterations in the renin-angiotensin-aldosterone axis have been reported in a subset of patients at presentation. Anecdotally, some patients with FGD have been initially diagnosed as having Addison's disease (AD), with implications for treatment and genetic counselling. Currently, mutations in three genes: the ACTH receptor (MC2R); the melanocortin 2 receptor accessory protein (MRAP); and the steroidogenic acute regulatory protein (STAR) are known to give rise to FGD types 1-3. We investigated a cohort of autoantibody-negative AD patients for mutations in these genes.MethodsForty patients with known AD without evidence of autoimmune disease were screened for mutations in MC2R, MRAP and STAR. In addition, patients were genotyped for the MC2R promoter polymorphism previously associated with reduced responsiveness to ACTH.ResultsNo mutations in MC2R, MRAP or STAR were identified in any patient. The frequencies of the MC2R promoter polymorphism were similar to those reported in healthy controls.ConclusionsFGD does not appear to be underdiagnosed in the AD population. However, in approximately 50% of patients with FGD, no genetic cause has yet been identified and it is possible that the other, as yet unidentified, genes giving rise to FGD may be implicated in AD.

| S-EPMC2808202 | biostudies-literature

Familial glucocorticoid deficiency with a point mutation in the ACTH receptor: a case report.

Project description:Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterized by severe glucocorticoid deficiency associated with failure of adrenal responsiveness to ACTH but no mineralocorticoid deficiency. We report a 2 month-old boy of nonconsanguineous parents, presented with hyperpigmentation. Physical examination showed diffuse dark skin of body including, oral mucosa, gum, hands, nails and scrotum. Laboratory evaluation revealed low serum cortisol (0.3 microg/dL), with very high plasma ACTH level (18,000 pg/mL), and serum cortisol level did not increase after ACTH stimulation test. Serum sodium, potassium, plasma renin activity, aldosterone and 17-hydroxyprogesterone were normal. Sequence analysis of the ACTH receptor (MC2R) gene showed a homozygous mutation of D103N. Diagnosis of FGD was made and treatment started with oral hydrocortisone.

| S-EPMC2752790 | biostudies-literature

Familial glucocorticoid deficiency presenting with generalized hyperpigmentation in an Egyptian child: a case report.

Project description:IntroductionFamilial glucocorticoid deficiency, or hereditary unresponsiveness to adrenocorticotropic hormone, is a rare autosomal recessive disease characterized by glucocorticoid deficiency in the absence of mineralocorticoid deficiency. It may present in infancy or early childhood with hyperpigmentation, failure to thrive, recurrent infections, hypoglycemic attacks and convulsions that may result in coma or death. Here, we report the case of an 18-month-old Egyptian boy with familial glucocorticoid deficiency.Case presentationAn 18-month-old Egyptian boy was referred to our institution for evaluation of generalized hyperpigmentation of the body associated with recurrent convulsions; one of his siblings, who had died at the age of nine months, also had generalized hyperpigmentation of the body. The initial clinical examination revealed generalized symmetrical deep hyperpigmentation of the body as well as hypotonia, normal blood pressure and normal male genitalia. He had low blood glucose and cortisol levels, normal aldosterone and high adrenocorticotropic hormone levels. Based on the above mentioned data, a provisional diagnosis of familial glucocorticoid deficiency was made, which was confirmed by a molecular genetics study. Oral hydrocortisone treatment at a dose of 10 mg/m2/day was started. The child was followed up after two months of treatment; the hyperpigmentation has lessened in comparison with his initial presentation and his blood sugar and cortisol levels were normalized.ConclusionFamilial glucocorticoid deficiency is a rare, treatable disease that can be easily missed due to nonspecific presentations. The consequences of delayed diagnosis and treatment are associated with high rates of morbidity and mortality.

| S-EPMC3369203 | biostudies-literature

Homozygous Rare PARN Missense Mutation in Familial Pulmonary Fibrosis.

Project description: Not available

| S-EPMC6423103 | biostudies-literature

A novel SCN9A gene variant identified in a Chinese girl with paroxysmal extreme pain disorder (PEPD): a rare case report.

Project description:BackgroundParoxysmal extreme pain disorder (PEPD) is a rare autosomal dominant hereditary disease, characterized by paroxysmal burning pain in the rectum, eyes or mandible and autonomic nervous symptoms, including skin redness and bradycardia. PEPD is a sodium channel dysfunctional disorder caused by SCN9A gene variants. It occurs mainly in Caucasians and only one case has been reported in the Chinese population. Here, we report the second PEPD case in a Chinese indivisual.Case presentationA 2 years and 6 months old girl initially presented with non-epileptic tonic seizures at 7 days after birth. Her clinical symptoms in order of presentation were non-epileptic tonic seizures, harlequin color change and pain. Genetic analysis showed the patient carried a heterozygous variant c.4384T>A (p.F1462I) in the SCN9A gene, which was speculated to cause PEPD symptoms. After administrating carbamazepine, the symptoms were relieved and the patient's condition improved. However, the patient's mother, who carries the same SCN9A variant as her daughter, only showed bradycardia and sinus arrest but no PEPD-related pain.ConclusionsThis is the second PEPD case reported in the Chinese population. With the discovery of a novel variant in SCN9A, we expanded the genotype spectrum of PEPD. This is the first case suggesting that the clinical presentations of SCN9A-associated PEPD may show inter familial phenotypic diversity. In the future of clinical diagnosis, patients with triggered non-epileptic tonic seizures or pain and harlequin color change should be considered for PEPD and proper and prompt treatment should be given.

| S-EPMC9287976 | 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