Clinical, biochemical and genetic features with nonclassical 21-hydroxylase deficiency and final height

Savaş‐Erdeve, Şenay; Çeti̇nkaya, Semra; Abalı, Zehra Yavaş; Poyrazoğlu, Şükran; Baş, Firdevs; Berberoğlu, Merih; Şıklar, Zeynep; Korkmaz, Özlem; Buluş, Derya; Akbaş, Emine Demet; Güran, Tülay; Böber, Ece; Akın, Onur; Yılmaz, Gülay Can; Aycan, Zehra

doi:10.1515/jpem-2017-0088

Cited by 19 publications

(35 citation statements)

References 21 publications

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“…A recent study from Portugal in which 60% of the patients were NC reported similar results 31 . Within the NC group, the frequency of p.V282L was similar to the frequencies observed in other countries ranging from 45% to 69.5% 17,18,31‐36 …”

Section: Discussionsupporting

confidence: 91%

Genetic characterization of a large cohort of Argentine 21‐hydroxylase Deficiency

Fernández

Taboas

Bruque

et al. 2020

Clinical Endocrinology

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Context 21‐hydroxylase deficiency is the most common cause of Congenital Adrenal Hyperplasia. It presents as severe or classical forms—salt wasting and simple virilizing—and a mild or nonclassical (NC). Several studies have reported the frequency of pathogenic variants in different populations, although few of them included a large number of NC patients. Objective To analyse the CYP21A2 gene defects in a large cohort of Argentine patients. Design Molecular characterization of 628 patients (168 classical, 460 nonclassical, representing 1203 nonrelated alleles), 398 relatives, 126 partners. Methods Genetic variants were assessed by allele‐specific PCR, PCR‐RFLP or direct sequencing. Deletions, duplications and large gene conversions (LGC) were studied by Southern blot/MLPA or long‐range PCR. Biological implications of novel variants were analysed by structure‐based in silico studies. Results The most frequent pathogenic variants were p.V282L (58%) in NC alleles and c.293‐13C>G (31.8%) and p.I173N (21.1%) in classical. Deletions and LGC were found at low frequency (6.2%), 57 alleles had rare pathogenic variants, and 3 had novel variants: p.(S166F); p.(P189R), p.(R436L). Genotype‐phenotype correlation was observed in 98.6% of the cases, 11 asymptomatic first‐degree relatives had pathogenic variants in both alleles, and 21/126 partners were carriers. Conclusions We conducted a comprehensive genetic characterization of the largest cohort of 21‐hydroxylase patients from the region. In particular, we add to the molecular characterization of a large number of NC patients and to the estimation of the disease carrier's frequency in our population.

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Section: Discussionsupporting

confidence: 91%

Genetic characterization of a large cohort of Argentine 21‐hydroxylase Deficiency

Fernández

Taboas

Bruque

et al. 2020

Clinical Endocrinology

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“…While it is well known that poor height prognosis in classical congenital hyperplasia patients could be significantly improved by the early start of appropriate glucocorticoid and mineralocorticoid replacement therapy, the same could not be fully confirmed for NCCAH patients [25]. Most of the studies about this topic in NCCAH, in fact, often showed unclear and discordant results [6-8, 12, 13].…”

Section: Discussion/conclusionmentioning

confidence: 99%

“…It emerged that the genotype could influence phenotype not only in classical form [27], but also in NCCAH, and that some kind of mutation could be responsible of a more severe or mild form of the disease [1, 8, 9, 23]. The data indicated that, NCCAH children with mild/severe genotype exhibited more accelerated growth, BA, and earlier puberty than those with mild/mild genotype, but their AH resulted lower.…”

Section: Discussion/conclusionmentioning

confidence: 99%

“…The main symptoms of the disease during childhood and adolescence include premature pubarche, cystic acne, hirsutism, and menstrual disorders [2, 5, 6]. In male patients, the disease may run as asymptomatic or poor-symptomatic, and the signs related to androgen excess might not always be clearly identifiable [7, 8]. Contrary to the classic form of 21-OH deficiency, no acceleration of intrauterine growth was detected in NCCAH subjects [9].…”

Section: Introductionmentioning

confidence: 99%

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Growth Trajectory and Adult Height in Children with Nonclassical Congenital Adrenal Hyperplasia

et al. 2020

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Background: Children with nonclassical congenital adrenal hyperplasia (NCCAH) often present increased growth velocity secondary to elevation of adrenal androgens that accelerates bone maturation and might compromise adult height (AH). Objective: The aim of the study was to analyze prognostic factors affecting growth trajectory (GT) and AH in children with NCCAH. Methods: The study was a retrospective, multicentric study. The study population consisted of 192 children with a confirmed molecular diagnosis of NCCAH, followed by pediatric endocrinology centers from diagnosis up to AH. Clinical records were collected and analyzed. AH (standard deviation score; SDS), pubertal growth (PG) (cm), GT from diagnosis to AH (SDS), and AH adjusted to target height (TH) (AH-TH SDS) were evaluated as outcome indicators using stepwise linear regression models. Results: The stepwise linear regression analysis showed that AH and AH-TH were significantly related to chronological age (CA) (p = 0.008 and 0.016), bone age (BA)/CA ratio (p = 0.004 and 0.001), height (H) (p < 0.001 for both parameters) at NCCAH Wasniewska et al.

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“…Sonuç olarak, non-klasik KAH hastası kızlar erken ergenlik, kıllanma artışı veya âdet düzensizliği bulgularıyla başvurabilirken erkeklerde belirgin bulgu olmadığından tanı gözden kaçabilir. Bu nedenle literatürde non-klasik KAH tanılı erkeklerin sayısı önemli ölçüde düşüktür (13,14) . Hastalığın OR geçiş göstermesi nedeniyle beklenen eşit cinsiyet dağılımına rağmen, çalışmamızda tüm non-klasik hastalarımızın kız cinsiyetli olması bu duruma bağlanabilir.…”

Section: Gereç Ve Yöntemunclassified

Frequency of enzyme deficiencies in patients with congenital adrenal hyperplasia: A single-center experience with 145 patients

Yildiz¹,

Önal²,

Aydın³

et al. 2019

IKSST

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polikistik over sendromu mevcuttu. 11β-hidroksilaz eksikliği olgularının yaklaşık yarısında hipertansiyon mevcuttu. POR eksikliği saptanan tek hastaya sendromik özelliklerinden dolayı Antley-Bixler sendromu tanısı konulmuştu. Sonuç: Merkezimizdeki KAH hastalarında gözlenen enzim eksikliği dağılımı literatür ile uyumlu bulunmuştur. 21-hidroksilaz eksikliği açısından mutasyon saptanmayan, hipertansiyon ve sendromik görünüm benzeri klinik özellikleri bulunan ve hormonal açıdan ipucu olan hastalar nadir KAH formları açısından değerlendirilmelidir.

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Clinical, biochemical and genetic features with nonclassical 21-hydroxylase deficiency and final height

Abstract: The final height of the patients who were treated during childhood was found to be shorter than the final height of patients during the adolescent period.

Cited by 19 publications

References 21 publications

Genetic characterization of a large cohort of Argentine 21‐hydroxylase Deficiency

Genetic characterization of a large cohort of Argentine 21‐hydroxylase Deficiency

Growth Trajectory and Adult Height in Children with Nonclassical Congenital Adrenal Hyperplasia

Frequency of enzyme deficiencies in patients with congenital adrenal hyperplasia: A single-center experience with 145 patients

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