Genotypic spectrum of 21-hydroxylase deficiency in an endogamous population

Mahmoud, Rana; Amr, Nermine Hussein; Toaima, Nadin N.; Kamal, Tarek M.; Elsedfy, Heba

doi:10.1007/s40618-021-01648-8

Cited by 3 publications

(1 citation statement)

References 47 publications

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“…By reviewing data from 48 articles including 119 patients from around the world, the present study aims to show the gender- and genotype-related prevalence of CAH, DSD, TARTs, and infertility in patients with heterozygous or homozygous POR gene variants. Genotype–phenotype correlation is sometimes a complex and attempted association and is still a matter of research, considering the most recent studies that have focused on mutations of the CYP21A2 gene [ 70 , 71 ]. This review allows a better understanding of the PORD phenotype.…”

Section: Discussionmentioning

confidence: 99%

Congenital adrenal hyperplasia, disorders of sex development, and infertility in patients with POR gene pathogenic variants: a systematic review of the literature

Gusmano

Cannarella

Crafa

et al. 2022

J Endocrinol Invest

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Background P450 oxidoreductase (POR) deficiency (PORD) is characterized by congenital adrenal hyperplasia (CAH) and disorders of sex development (DSD) in both sexes. PORD can also associate with skeletal defects. However, the prevalence of these phenotypes is unknown. Aim To evaluate the prevalence of CAH, DSD, and infertility of patients with POR gene pathogenic variants by a systematic review of the literature. Methods The literature search was performed through PubMed, MEDLINE, Cochrane, Academic One Files, Google Scholar, and Scopus databases. All studies reporting information on CAH, DSD, testicular adrenal rest tumor (TARTs), and fertility in patients with POR gene pathogenic variants were included. Finally, the prevalence of abnormal phenotypes was calculated. Results Of the 246 articles initially retrieved, only 48 were included for a total of 119 (46 males and 73 females) patients with PORD. We also included the case of a male patient who consulted us for CAH and TARTs but without DSD. This patient, found to be a carrier of combined heterozygous POR mutation, reached fatherhood spontaneously. All the patients found had CAH. The presence of DSD was found in 65.2%, 82.1%, and 82.1% of patients with compound heterozygosity, homozygosity, or monoallelic heterozygous variants, respectively. The prevalence was significantly higher in females than in males. The prevalence of TARTs in patients with PORD is 2.7%. Only 5 women with PORD became pregnant after assisted reproductive techniques and delivered a healthy baby. Except for the recently reported proband, no other studies focused on male infertility in patients with POR gene variants. Conclusion This systematic review of the literature reports the prevalence of CAH, DSD, and TARTs in patients with PORD. The unknown prevalence of POR gene pathogenetic variants and the paucity of studies investigating fertility do not allow us to establish whether PORD is associated with infertility. Further studies on both women and men are needed to clarify this relationship.

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Section: Discussionmentioning

confidence: 99%

Congenital adrenal hyperplasia, disorders of sex development, and infertility in patients with POR gene pathogenic variants: a systematic review of the literature

Gusmano

Cannarella

Crafa

et al. 2022

J Endocrinol Invest

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Targeted long-read sequencing for comprehensive detection of CYP21A2 mutations in patients with 21-hydroxylase deficiency

Zhang,

Gao,

et al. 2023

J Endocrinol Invest

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Gonadal changes in children and adolescents with congenital adrenal hyperplasia

Mahmoud,

Abdelrahman,

Mohamed

et al. 2024

Journal of Pediatric Endocrinology and Metabolism

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Objectives Testicular adrenal rest tumours (TARTs) are a common cause of infertility in males with congenital adrenal hyperplasia (CAH). Ovarian adrenal rest tumours (OARTs) and polycystic ovaries (PCO) can impair ovarian function in female patients with CAH. We aim to detect gonadal changes in children and adolescents with CAH. Methods This study was conducted on 50 CAH patients (30 females and 20 males) with 21-hydroxylase deficiency (21-OHD), with a mean age of 10.35 ± 2.36 years. Testicular ultrasonography and pelvic magnetic resonance imaging (MRI) were done in males and females respectively. Glucocorticoid doses and biochemical data were obtained from the patients’ medical records. Results TARTs were detected in 10/20 male patients (50 %). There was a significant relation between presence of TARTs, body mass index (BMI) standard deviation score (SDS), and bone age (p=0.017 and 0.023; respectively). There was no significant relation between presence of TARTs, laboratory parameters, or treatment received (p>0.05). Of those subjected to genetic analysis, 48 % had I2 splice (c.290-13A/C>G) followed by P30L (c.89C>T) (40.7 %). P30L (c.89C>T) was the most common allele among the patients with TARTs (42.9 %). There was no significant relation between presence of TARTs, the genotype, alleles, or the genotype groups (p>0.05). Only one female patient had radiological evidence of bilateral polycystic ovaries and none had OARTs. Conclusions The prevalence of TARTs in our study was high (50 %). Screening for TARTs in males with CAH is crucial; however, routine ovarian imaging in CAH females is not indicated unless ovarian dysfunction is present.

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Genotypic spectrum of 21-hydroxylase deficiency in an endogamous population

Cited by 3 publications

References 47 publications

Congenital adrenal hyperplasia, disorders of sex development, and infertility in patients with POR gene pathogenic variants: a systematic review of the literature

Congenital adrenal hyperplasia, disorders of sex development, and infertility in patients with POR gene pathogenic variants: a systematic review of the literature

Targeted long-read sequencing for comprehensive detection of CYP21A2 mutations in patients with 21-hydroxylase deficiency

Gonadal changes in children and adolescents with congenital adrenal hyperplasia

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