Background: Deficiency of 17α-hydroxylase/17,20-lyase is a rare cause of 46,XY disordered sex development.Objective: We characterize in vitro and in vivo effects of two novel CYP17A1 gene mutations identified in a patient with a mild phenotype of CYP17A1 deficiency.Subjects and methods: A 46,XY patient presented with ambiguous genitalia. CYP17A1 deficiency was suspected at 2 months on the basis of steroid analysis performed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). Mutational analysis of the CYP17A1 gene was performed by PCR and Sanger sequencing. To characterize the effect of CYP17A1 mutation on 17α-hydroxylase and 17,20-lyase activities in vitro, HEK293 cells were transiently transfected with CYP17A1 expression plasmids, incubated with progesterone or 17-OH-pregnenolone and concentrations of 17-OH-progesterone or DHEA were then measured in the cell culture medium by LC–MS/MS.Results: Clinical and hormonal findings in the patient were consistent with partial combined deficiency of 17α-hydroxylase/17,20-lyase. The sequencing of the CYP17A1 gene in the patient revealed compound heterozygosity for two novel mutations: c.107delT p.R36fsX107 and p.W121R. After 6-h in vitro culture of transfected HEK293 cells in the presence of 1 μM progesterone, 17α-hydroxylase activity of p.W121R mutant was 60.5±16.3%, while 17,20-lyase activity of mutant measured from the amount of DHEA produced in the presence of 1 μM of 17-OH-pregnenolone was 15.8±2.6% compared with the WT.Conclusions: p.W121R substitution, affecting the first residue in the conserved heme-interacting WXXXR motif of CYP17A1, is associated with partial combined deficiency of 17α-hydroxylase/17,20-lyase.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive diseases characterized by a defect in one of the enzymes or transport proteins involved in the cortisol synthesis in the adrenal cortex. The most common form of CAH, which occurs in more than 90% of cases, is a 21-hydroxylase enzyme deficiency. The latter is subdivided into nonclassical and classic (salt-losing and virilizing) forms. The prevalence of classic forms of 21-hydroxylase deficiency ranges from 1: 14,000 to 1:18,000 live births worldwide. According to the data of neonatal screening in the Russian Federation, the prevalence of the disease in some regions ranges from 1: 5000 to 1: 12000, in the country as a whole - 1: 9638 live newborns. The non-classical form of CAH occurs more often - from 1: 500 to 1: 1000 among the general population. In second place is the hypertensive form of CAH - a deficiency of 11β-hydroxylase, which, according to the literature, occurs in about 1 per 100,000 newborns. These clinical guidelines were compiled by a professional community of narrow specialists, approved by the expert council of the Ministry of Health of the Russian Federation, and updated the previous version published in 2016. The clinical guidelines are based on systematic reviews, meta-analyses and original articles, and scientific work on this issue in the Russian Federation and other countries. The purpose of this document is to provide clinicians with the most up-to-date, evidence-based guidelines for the CAH diagnosis and treatment

The precocious puberty is an urgent problem of pediatric endocrinology characterized by clinical and pathogenetic heterogeneity. The appearance of secondary sex characteristics before the age of 8 years in girls and 9 years in boys requires timely diagnosis and the appointment of pathogenetically justified treatment in order to achieve the target indicators of final growth and prevent social deprivation. The developed clinical guidelines are the main working tool of the practitioner. They briefly and structurally present the main information about the epidemiology and modern classification of рrecocious puberty, methods of its diagnosis and treatment based on the principles of evidence-based medicine.

Background: Although the importance of steroidogenic factor-1 (SF1, NR5A1) for adrenal development is supported by numerous in vitro and in vivo studies, cases of

Here, we report a clinical case of isolated papillary thyroid cancer associated with a germline DICER1 gene mutation in a boy and his father. The father underwent surgery for a euthyroid multinodular goiter at the age of 7 and 9 years. On examination at the age of 27 years, he was diagnosed with papillary thyroid cancer. At the age of 7 years, the boy was suspected of having a multinodular goiter (based on thyroid ultrasonography findings); he underwent total thyroidectomy. A histological examination of the surgical material revealed encapsulated papillary carcinoma. Neither boy nor his father had been exposed to radiation or chemotherapy before the diagnosis of papillary thyroid cancer. To clarify the etiology of disease, a molecular genetic testing was performed using next-generation sequencing (NGS). The proband and his parent had a heterozygous thymine deletion in the exon 4 at position 380, which led to a shift in the reading frame with the formation of a premature stop codon (c.380delT p.L127QfsX3).

Hypophosphatasia (HPP) is a rare hereditary metabolic disease characterized by defective bone and dental mineralization, systemic complications that lead to disability of patients. HPP is classified into six forms according to the age of onset and severity of its clinical picture. The disease is caused by a reduced activity of the tissue nonspecific alkaline phosphatase (TNSALP) and elevated concentrations of pyrophosphates. Asfotase alfa is the only pathogenetic enzyme replacement therapy with recombinant human bone-targeted TNSALP approved for treatment of patients with perinatal, infantile and juvenile‐onset HPP. This treatment is associated with improved skeletal mineralization, respiratory function and overall survival in infants and young children with life-threatening hypophosphatasia. The world experience in application of recombinant alkaline phosphatase in adults is very limited. We present a clinical case that describes the first Russian experience in the use of asfotase alfa in an 18-year-old patient with late diagnosis of childhood-onset HPP.