Clinical, molecular and histopathological features of short stature syndrome with novel CUL7 mutation in Yakuts: new population isolate in Asia.

BACKGROUND: In total, 43 patients having short stature syndrome in 37 Yakut families with autosomal recessive prenatal and postnatal nonprogressive growth failure and facial dysmorphism but with normal intelligence have been identified. METHODS: Because Yakuts are considered as a population isolate and the disease is rare in other populations, genomewide homozygosity mapping was performed using 763 microsatellite markers and candidate gene approach in the critical region to identify the causative gene for the short stature syndrome in Yakut. RESULTS: All families shared an identical haplotype in the same region as the identical loci responsible for 3-M and gloomy face syndromes and a novel homozygous 4582insT mutation in Cullin 7 (CUL7) was found, which resulted in a frameshift mutation and the formation of a subsequent premature stop codon at 1553 (Q1553X). Yakut patients with short stature syndrome have unique features such as a high frequency of neonatal respiratory distress and few bone abnormalities, whereas the clinical features of the other Yakut patients were similar to those of 3-M syndrome. Furthermore, abnormal vascularisation was present in the fetal placenta and an abnormal development of cartilage tissue in the bronchus of a fetus with CUL7 mutation. CONCLUSION: These findings may provide a new understanding of the clinical diversity and pathogenesis of short stature syndrome with CUL7 mutation.

[Phylogenetic analysis of ancient mitochondrial DNA lineages of human remains found in Yakutia].

Molecular genetic analysis of ancient human remains are mostly based on mitochondrial DNA due to its better preservation in human skeletons in comparison with nuclear DNA. We investigated mtDNA extracted from human skeletons found in graves in Yakutia to determine their haplotypes and to compare them with lineages of modern populations. Ancient DNA was extracted from fragments of three skeletons of Yakut graves at At-Dabaan, Ojuluun and Jaraama sites (dating XVIII century) and two skeletons of Neolithic graves at Kerdugen site found in central Yakutia (Churapchinsky, Kangalassky and Megino-Kangalassky districts of Yakutia). Five different haplotypes belonging to specific Asian haplogroups were identified. Lineages of mtDNA of Yakut graves belong to haplo-groups C4a, D5a2 and B5b. Our results indicate the continuity of mitochondrial lineages in the Yakut gene pool during the last 300 years. Haplotypes of two humans from Kerdugen site graves belong to haplogroups A4 and G2a/D. We compared these haplotypes with that of 40,000 Eurasian individuals, 900 of them from Yakutia. No exact matches were found in Paleoasian populations of Chukchi, Eskimos, Koryaks and Itelmen. Phylogenetically close haplotypes (+/- 1 mutation) were found in populations of Yakuts and Evenks, as well as in some populations of China, Southern and Western Siberia.

Monitoring of aortic and coronary atherosclerosis in native and non-native males of Yakutsk over 40 years.

We have analyzed the development of aortic and coronary atherosclerosis over 40 years in native and non-native males of Yakutsk by comparing the data obtained in 1963-1965, 1985-1987 and 2001-2003. The research was carried out in compliance with the WHO program for the atherosclerosis epidemiology studies using autopsy material. Subjects (361 natives and 692 non-natives) included in the research died of external causes at the age of 20-59 years and had no history of chronic diseases, which was confirmed by post-mortem examination. The prevalence and the extent of raised atherosclerotic lesions (fibrous plaques, complicated lesions and calcinosis) in the aorta and coronary arteries were determined by visual planimetry after staining with Sudan IV. An accelerated development of aortic and coronary atherosclerosis was revealed in both populations throughout the entire period of 40 years with more severe manifestations in non-native males. The severity of atherosclerosis increased considerably in native and non-native males aged over 40 years. The rate of the increase in the extent of raised atherosclerotic lesions tended to be greater in native than in non-native males.

[A 40-year study of aortic and coronary artery atherosclerosis in male population of Yakutsk].

The trends in development of aortic and coronary atherosclerosis in healthy male population were studied by WHO methods in three trials: in 1963-1965, 1985-1987, 2001-2003. It was found that atherosclerosis and coronary arteries stenosis were less frequent in the native population of Yakutia than in migrants.

[The clinical and morphological features of pulmonary tuberculosis under the conditions of the Far North].

The clinical and morphological features of pulmonary tuberculomas were studied in 205 patients among the naives and newcomers of the Far North. It was established that the lymphohematogenous spread of tuberculosis involving mainly the lymphatic system into the inflammatory process predominates in the genesis of tuberculomas under the conditions of the Far North. At the same time the lymphatic genesis of tuberculosis was found to affect the development of pulmonary tuberculomas in 60% of cases among the native patients. In most patients, the afflicted intrathoracic lymph nodes became a source of retrograde dissemination of tuberculosis in the lung. Tuberculomas were chiefly unilateral and in 56.7% of cases they were located in the lower portions of the lung in the presence of significant fibrosis. The lymphohematogenous spread of tuberculous infection was a cause of pulmonary tuberculomas in most (72.9%) newcomers on adapting to the conditions of the Far North. In most cases, tuberculomas were formed from a newly appeared tuberculous focus in the presence of intact lung tissue and located in the upper portions of both lungs. The formed tuberculomas had no extensive focal dissemination and were present within the anatomic structure of one or two segments of the lung.

[Atherosclerosis of the aorta and coronary arteries in men living in Iakutia (an epidemiologic pathologo-anatomical study)]. / Ateroskleroz aorty i koronarnnykh arterii u muzhchin, 6rozhivaiushchikh v Iakutii (épidemiologicheskoe patologoanatomicheskoe issledovanie.

A quantitative study was made of atherosclerosis in the aorta and coronary arteries in 3 groups of 20-59-year old male patients: (1) aborigines such as Yakuts, Chukchi, Evenks; (2) those born in the North (Russians born in Yakutia); and (3) new comers (120, 103, and 233 cases, respectively) after Sudan IV staining of the aortas and coronary arteries. The frequency and extent of fatty streaks, fibrous plaques, complicated lesions, and calcinosis were determined. The severity of atherosclerosis was found to be slightest in the aborigines; differences between those born in the North and new comers were small; yet coronary stenoses (greater than or equal to 50% of the lumen) were substantially more common in the former. Aortic intimal rhythmic structures were significantly more frequently detected in the aborigines than in those born in the North and new comers. The age-specific parameters for the abdominal aorta in the age groups of 20-59 years were 58.9, 37.0, and 39.8%, respectively.