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An Atypical Case of Familial Glucocorticoid Deficiency without Pigmentation Caused by Coexistent Homozygous Mutations in MC2R (T152K) and MC1R (R160W)

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dc.contributor.authorBEREKET, ABDULLAH
dc.contributor.authorsTuran, Serap; Hughes, Claire; Atay, Zeynep; Guran, Tulay; Haliloglu, Belma; Clark, Adrian J. L.; Bereket, Abdullah; Metherell, Louise A.
dc.date.accessioned2022-03-14T10:04:30Z
dc.date.available2022-03-14T10:04:30Z
dc.date.issued2012-05-01
dc.description.abstractContext: Familial 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). Objective: The aim of the study was to determine the cause of a nonhyperpigmented case of FGD. Patients: The 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. Results: Nucleotide 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. Conclusion: We 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. (J Clin Endocrinol Metab 97: E771-E774, 2012)
dc.identifier.doi10.1210/jc.2011-2414
dc.identifier.issn0021-972X
dc.identifier.pubmed22337906
dc.identifier.urihttps://hdl.handle.net/11424/244006
dc.identifier.wosWOS:000303915900010
dc.language.isoeng
dc.publisherENDOCRINE SOC
dc.relation.ispartofJOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectMELANOCORTIN 1 RECEPTOR
dc.subjectADDISONS-DISEASE
dc.subjectRED HAIR
dc.subjectADRENOCORTICOTROPIN RECEPTOR
dc.subjectADRENAL INSUFFICIENCY
dc.subjectVARIANTS
dc.subjectHYPERPIGMENTATION
dc.subjectHUMANS
dc.subjectTYPE-1
dc.subjectGENE
dc.titleAn Atypical Case of Familial Glucocorticoid Deficiency without Pigmentation Caused by Coexistent Homozygous Mutations in MC2R (T152K) and MC1R (R160W)
dc.typearticle
dspace.entity.typePublication
local.avesis.id9cb7b985-4267-405d-a120-a9b09cdf7efe
local.import.packageSS16
local.indexed.atWOS
local.indexed.atSCOPUS
local.indexed.atPUBMED
local.journal.numberofpages4
oaire.citation.endPageE774
oaire.citation.issue5
oaire.citation.startPageE771
oaire.citation.titleJOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
oaire.citation.volume97
relation.isAuthorOfPublication669e9474-4e39-453f-a4bc-4ede9cb5abac
relation.isAuthorOfPublication.latestForDiscovery669e9474-4e39-453f-a4bc-4ede9cb5abac

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