BackgroundPrimary microcephaly represents an example of clinically and genetically heterogeneous condition. Here we describe a case of primary microcephaly from the Karachay-Cherkess Republic, which was initially diagnosed with Seckel syndrome.Case presentationClinical exome sequencing of the proband revealed a novel homozygous single nucleotide deletion in ASPM gene, c.1386delC, resulting in preterm termination codon. Population screening reveals allele frequency to be less than 0.005. Mutations in this gene were not previously associated with Seckel syndrome.ConclusionsOur case represents an additional support for the clinical continuum between Seckel Syndrome and primary microcephaly.

Prevalence and allelic heterogeneity of hereditary diseases (HDs) could vary significantly in different human populations. Current knowledge of HDs distribution in populations is generally limited to either European data or analyses of isolated populations which were performed several decades ago. Thus, an acknowledgement of the HDs prevalence in different modern open populations is important. The study presents the results of a genetic epidemiological study of hereditary diseases (HDs) in the population of the Karachay-Cherkess Republic (KChR). Clinical screening of a population of 410,367 people for the identification of HDs was conducted. The population surveyed is represented by five major ethnic groups—Karachays, Russians, Circassians, Abazins, Nogais. The study of the populations was carried out in accordance with the proprietary protocol of genetic epidemiological examination designed to identify >3500 HDs easily diagnosed during clinical examination by qualified specialists specializing in the HDs. The protocol consists of the population genetic and medical genetic sections and is intended for comprehensive population analysis based on the data on different genetic systems, including the genes of HDs, DNA polymorphisms, demographic data collected during hospital-based survey. 8950 families (with 10,125 patients) with presumably the HDs were initially identified as a result of the survey and data collection through various sources of registration (from 1156 medical workers from 163 medical institutions). A diagnosis of hereditary pathology was established in 1849 patients (from 1295 families). Two hundred and thirty nosological forms were revealed (in 1857 patients from 1295 families). The total prevalence of HDs was 1:221. Differences between populations and ethnic groups were identified: 1:350 in Russians, 1:195 in Karachays, 1:199 in Circassians, 1:218 in Abazins, 1:135 in Nogais. Frequent diseases were determined, the presence of marked genetic heterogeneity was identified during the confirmatory DNA diagnosis. To explain the reasons for the differentiation of populations by load of HD, a correlation analysis was carried out between the FST (random inbreeding) in populations and HDs load values. This analysis showed genetic drift is probably one of the leading factors determining the differentiation of KChR populations by HDs load. For the first time, the size of the load and spectrum of HDs in the populations of the KChR are determined. We have demonstrated genetic drift to be one of the main factors of the population dynamics in studied population. A significant genetic heterogeneity of HDs, both allelic and locus, was revealed in KChR.

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Physics and Technology, Dolgoprudny, 5 Pirogov Russian National Research Medical University, Moscow, renazinchenko@mail.ru The paper considers addresses an age-sex structure of urban and rural populations of Karachay-Cherkess Republic and evaluated the load of hereditary diseases in three age cohorts of the population -pre-productive, reproductive and post-productive. Pre-productive population group is the smallest one and does not exceed one quarter in both urban and rural population. The most numerous group -the reproductive population -is approximately 2/5 of the nominal payroll. The graphical analysis shows all the socio-economic upheavals of the last century, which affect the reproductive behavior of the population. Every an urban women of reproductive age haves 0,98 children on the average, while children of rural one -1,14. The load of monogenic hereditary pathology is highest in the pre-productive age group (of 11.57 cases per 1000 people in the rural population) , below while the lowest is all -in the post-productive cohort (1.43 cases per 1000 in urban population). The data allow us to estimate the necessary amount of medical and genetic services in different age cohorts of the population. Keywords: age and sex structure, the load of monogenic hereditary pathology, Karachay-Cherkessia Republic.