Nonclassic Congenital Adrenal Hyperplasia (NCCAH) Due to 21-Hydroxylase Deficiency: Clinical Management and Genetic Counseling of Two Portuguese Families

Lurdes de Matos, Maria; Antunes, Diana; Gonçalves, João; Lopes, Lurdes; Kay, Teresa

Publication

Nonclassic Congenital Adrenal Hyperplasia (NCCAH) Due to 21-Hydroxylase Deficiency: Clinical Management and Genetic Counseling of Two Portuguese Families

2016-04Conference object

dc.contributor.author	Lurdes de Matos, Maria
dc.contributor.author	Antunes, Diana
dc.contributor.author	Gonçalves, João
dc.contributor.author	Lopes, Lurdes
dc.contributor.author	Kay, Teresa
dc.date.accessioned	2017-02-21T13:56:35Z
dc.date.available	2017-02-21T13:56:35Z
dc.date.issued	2016-04
dc.description.abstract	Introduction: Congenital adrenal hyperplasia (CAH) due to 21-Hydroxylase deficiency occurs in 90-95% of cases, being a common autosomal recessive condition that can present with a wide range of hyperandrogenemic signs in childhood or adulthood. Severity of this disease is correlated with the enzymatic blockade of 21-Hydroxylase which depends of the mutation in gene CYP21A2. Two clinical forms are possible: classic, subdivided in salt-wasting and simple virilizing form (severe) and nonclassic or late onset (less severe). Aims: We studied two portuguese families with NCCAH due to 21-Hidroxilase deficiency in order to improve clinical management and genetic counseling of their members. Methods: Clinical presentation and hormonal assays (including test of tetracosactide) were performed in index cases (IC) . Genomic DNA of each family member was sequenced for the 9 most frequent mutations in CYP21A2. Total deletion of CYP21A , conversion in non functioning CYP21A1P or CYP21A1P_ CYP21A2 quimeras were also analyzed by enzymatic restriction. Results: Family 1- IC: Female, 31 years old with NCCAH diagnosed at age 6 , after investigation of precocious pubarche and with test of tetracosactide positive (17-alpha hydroxyprogesterone levels > 10-15 ng/ml) . Molecular study of CYP21A2 showed a mutation g.1683G> T , homozygous , in CYP21A2 and a non functioning allele of CYP21A2 , heterozygous (non severe 21-Hidroxilase deficiency). Mother was carrying a non functioning allele of CYP21A2 , heterozygous (severe); Father, Brother and Partner were heterozygous for mutation g.1683G> T (non severe). Family 2- IC: Female, 45 years old presenting hirsutism and oligoamenorrhea at age 35 and with test of tetracosactide positive confirming NCCAH Genetic study identified mutation g.1683G> T (less severe) in a copy and g.655A/C>G in another copy (splicing mutation severe). Familial genetic study identified two sisters (age 36 and age 40), asymptomatic but with pathologic genotype confirming NCCAH.	pt_PT
dc.description.version	info:eu-repo/semantics/publishedVersion	pt_PT
dc.identifier.uri	http://hdl.handle.net/10400.18/4324
dc.language.iso	eng	pt_PT
dc.peerreviewed	yes	pt_PT
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	pt_PT
dc.subject	21-Hydroxylase	pt_PT
dc.subject	Nonclassic CAH	pt_PT
dc.subject	CYP21A2	pt_PT
dc.subject	Congenital Adrenal Hyperplasia (CAH)	pt_PT
dc.subject	salt-wasting	pt_PT
dc.subject	Simple Virilizing	pt_PT
dc.subject	Doenças Genéticas	pt_PT
dc.title	Nonclassic Congenital Adrenal Hyperplasia (NCCAH) Due to 21-Hydroxylase Deficiency: Clinical Management and Genetic Counseling of Two Portuguese Families	pt_PT
dc.type	conference object
dspace.entity.type	Publication
oaire.citation.conferencePlace	Boston, Massachusetts, United States.	pt_PT
oaire.citation.title	98th Annual Meeting and Expo of the Endocrine Society (ENDO), 1-4 April 2016	pt_PT
rcaap.rights	openAccess	pt_PT
rcaap.type	conferenceObject	pt_PT