[Clinical and laboratory characteristics of arginine vasopressin resistance, caused by a new homozygous mutation p.R113C in AQP2].

Congenital nephrogenic diabetes insipidus (CNDI, arginine vasopressin resistance) is a rare inherited disorder characterized by insensitivity of the kidney to the antidiuretic effect of vasopressin. NDI is clinically characterized by polyuria with hyposthenuria and nocturia and polydipsia. In the majority of cases, about 90%, nephrogenic diabetes insipidus is an X-linked recessive disorder caused by mutations in the AVP V2 receptor gene (AVPR2). In the remaining cases, about 10%, the disease is autosomal recessive or dominant and, for these patients, mutations in the aquaporin 2 gene (AQP2) have been reported. To date, the nucleotide variants registered in AQP2 were sporadic, there is no data on the presence of «frequent¼ mutations and the prevalence of the disease both among the global population and among individual ethnic groups. In this paper, we describe 12 cases of arginine vasopressin resistance caused by a new homozygous mutation p.R113C in AQP2 presented among the indigenous population of the Republic of Buryatia.

[Clinical guideline of «congenital hypothyroidism¼].

Congenital hypothyroidism is an important issue of pediatric endocrinology at which timely diagnosis and treatment can prevent the development of severe cases of the disease. The developed clinical guidelines are a working tool for a practicing physician. The target audience is pediatric endocrinologists and pediatricians. They briefly and logically set out the main definition of the disease, epidemiology, classification, methods of diagnosis and treatment, based on the principles of -evidence-based medicine.

[Kalmann syndrome in monozygous twins as an isolated manifestation of the SOX10 gene defect].

More than 30 genes are known to take part in hypothalamic-pituitary-gonadal axis development at the date and role of more than 10 other genes is studied. Despite it about 50% of isolated hypogonadotropic hypogonadism cases still have no molecular genetic explanation.A number of specific associations between iHH and different not-reproductive manifestations called syndromic forms are distinguished in general group of iHH. For example, the combination of Kalmann syndrome with sensorineural hearing loss is known as manifestation for defects of some genes encoding factors of neuronal migration; in patients with this phenotype CHD7, SOX10 genes defects are most frequent. However, defects in the genes of neuronal migration factors are characterized by a wide variability of phenotype, which is explained by the epigenetic mechanisms influence. Carriers of the mutation within the same family may lack some non-reproductive manifestations as well as hypogonadism.Here we present a case of Kalmann syndrome in monozygous twins, caused by a previously not described heterozygous mutation c.462C> G: p.I154M in the SOX10 gene in the absence of sensorineural hearing loss. The mutation was inherited from a father who has only isolated anosmia in the phenotype. This mutation was identified during full exome sequencing. This unique observation for Russia shows on the one hand expediency to check SOX10 sequence in addition to the other factors of neuronal migration and differentiation and, on the other hand, the prospect of full exome sequencing in a group of patients with undifferentiated iHH.

[Clinical and molecular genetic features of 3 family cases of the central precocious puberty, due to MKRN3 gene defects].

Gonadotropin-dependent precocious puberty (central) is a condition resulting from the early (up to 8 years in girls and 9 years in boys) reactivation of the hypothalamic-pituitary-gonadal axis. An increase in the secretion of sex steroids by the gonads in this form is a consequence of the stimulation of the sex glands by gonadotropic hormones of the pituitary gland. In the absence of central nervous system abnormalities, CPP is classified as idiopathic and as familial in some cases, emphasizing the genetic origin of this disorder. Loss-of-function mutations in Makorin Ring Finger Protein 3 (MKRN3) are the most common identified genetic cause of central precocious puberty compared to sporadic cases. In the present study we performed the first descrition of 3 family cases of central precocious puberty duo to novel MKRN3 gene mutation detected by NGS in the Russian Federation.

[Clinical and molecular genetic features of cases of isolated hypogonadotropic hypogonadism, associated with defects in GNRHR genes].

Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder characterised by lack of pubertal development and infertility, due to deficient production, secretion or action of gonadotropin-releasing hormone (GnRH). Clinically, there are variants of CHH with hypo-/anosmia (Kalman syndrome) and normosmic hypogonadotropic hypogonadism. Given a  growing list of gene mutations accounting for CHH, the application of next generation sequencing (NGS) comprises an excellent molecular diagnostic approach because it enables the simultaneous evaluation of many genes. Biallelic mutations in GNRHR gene lead to the development of hypogonadotropic hypogonadism with normosmia. In this paper, we describe 16 patients with proven GnRH resistance and estimate the frequency of pathogenic variants in the GNRHR gene in the Russian population.