HINT1 gene pathogenic variants: the most common cause of recessive hereditary motor and sensory neuropathies in Russian patients

Pathogenic variants in the HINT1 gene lead to hereditary axonopathy with neuromyotonia. However, many studies show that neuromyotonia may remain undiagnosed, while axonopathy is the major clinical finding. The most common cause of neuromyotonia and axonopathy, especially in patients of Slavic origin, is a c.110G>C (p.Arg37Pro) pathogenic variant in homozygous or compound heterozygous state. In this study, we analyzed a peripheral neuropathy caused by pathogenic variants in the HINT1 gene and evaluated its contribution to the hereditary neuropathy structure. The studied group included 1596 non-related families diagnosed with hereditary motor and sensory neuropathy (HMSN). The results show that HINT1 gene pathogenic variants make a significant contribution to the hereditary neuropathy epidemiology in Russian patients. They account for at least 1.9% of all HMSN cases and 9% of axonopathy cases. The most common HINT1 pathogenic variant in Russian patients is the c.110G>C (p.Arg37Pro) substitution. Its allelic frequency is 0.2% (95% CI 0.19–0.21%), carrier frequency is 1 in 250 people in Russian Federation, and the estimated disease incidence is 1 in 234,000 individuals. It was determined that the cause of this pathogenic variant’s prevalence is the founder effect.

     

Local adaptation in populations of a Brachionus group plicatilis cryptic species inhabiting three deep crater lakes in Central Mexico

1. Salinity is a strong selective force for many aquatic organisms, affecting both ecological and evolutionary processes. Most of our knowledge on the effects of salinity on rotifers in the Brachionus plicatilis species complex is based mainly on populations from waterbodies that experience broad environmental changes both seasonally and annually. We tested the hypothesis that, despite the supposedly high potential for gene flow among rotifers inhabiting neighbouring environments, constant salinity has promoted local adaptation, genetic population divergence and even cryptic speciation in B. plicatilis complex populations from three deep maar lakes of distinct salinities [1.1, 6.5 and 9.0 g L^?1 total dissolved solids (TDS)] in Central Mexico. 2. To look for local adaptation, we performed common garden experiments to test the effect of different salinities on population density and intrinsic growth rate (r). Then, we evaluated the genetic divergence by sequencing the cytochrome c oxidase subunit I (COI) gene and performed reproductive trials to assess the potential gene flow among the three populations and with other closely related B. plicatilis complex species. 3. We confirmed that the rotifer populations have phenotypic plasticity in tolerance of salinity, but only rotifers from the least saline lake are adapted to low salinity. Among the populations, sequence divergence at COI was very low (just a single haplotype was found), suggesting a persistent founder effect from a relatively recent single colonisation event and a subsequent dispersal from one lake to the others, and a very restricted immigration rate. In the phylogenetic analysis, rotifers from this area of Mexico clustered in the same clade with the middle‐sized species Brachionus ibericus and B. sp. ‘Almenara’. Mexican rotifers showed successful recognition, copulation and formation of hybrids among them, but interpopulation breeding with the Spanish B. ibericus and B. sp. ‘Almenara’ was unsuccessful. 4. We conclude that the B. plicatilis complex populations from these three lakes belong to a new biological species not yet described (presently named B. sp. ‘Mexico’). To our knowledge, this is the first report of local adaptation of a natural B. plicatilis complex population living in freshwater conditions (1.1 g L^?1 TDS).     

Heterozygous carrier rate for type I–IV proximal spinal muscular atrophy in Chuvashes, Udmurts, and residents of the Moscow region

The first estimation of the heterozygous carrier rates for the SMN1 gene deletions and SMN2 gene duplications in populations of Russia has been performed. The numbers of SMN gene copies have been deter-mined in samples from Chuvash and Udmurt populations, as well the population of the Moscow region, by means of multiplex ligation-dependent probe amplification. The heterozygous carrier rates for the CMA gene were 2.7% (1: 37 people), 2.8% (1: 36 people), and 2.8% (1: 36 people) in Chuvashes, Udmurts, and residents of the Moscow region, respectively. The SMN2 duplication frequencies have been determined in the studied groups. It is 1.5, 4, and 2.5% in Chuvashes, Udmurts, and residents of the Moscow region, respectively. The high SMN2 duplication frequency in Udmurts may explain why the SMN1 heterozygous carriage frequency in this population was overestimated in earlier PCR-RFLP analyses.     

The spectrum of CLCN1 gene mutations in patients with nondystrophic Thomsen’s and Becker’s myotonias

Thomsen??s and Becker??s diseases are the most prevalent nondystrophic myotonias. Their frequency varies, according to different sources, from 1: 100000 to 1: 10000. Thomsen??s myotonia is autosomal dominant, and Becker??s myotonia is autosomal recessive. Both diseases result from mutations of the CLCN1 gene encoding chloride ion channels of skeletal muscles. Molecular genetic analysis of the CLCN1 gene has been performed in patients with diagnoses of nondystrophic Thomsen??s and Becker??s myotonias living in the Russian Federation. A sample of 79 unrelated probands with nondystrophic Thomsen??s and Becker??s myotonias and 44 their relatives has been formed in the Laboratory of DNA Diagnosis of the Medical Genetic Research Center of the Russian Academy of Medical Sciences. Forty CLCN1 gene mutations have been found in a total of 118 chromosomes of 66 probands, including 21 familial and 45 sporadic cases. About half the mutations detected (45%) have been found for the first time; they are not described in the SNP database (ncbi.nlm.nih.gov). The following mutations (substitutions) have been detected in more than one chromosome, accounting for a total of 59.3% of chromosomes with mutations: Gly190Ser (5.9%), c.1437_1450del14 (9.3%), Ala493Glu (5.1%), Thr550Met (3.4%), Tyr686Stop (5.1%), and Arg894Stop (30.5%).     

Genetic epidemiological study of Bashkortostan Republic: The diversity of monogenic hereditary diseases in five districts

The diversity of monogenic hereditary diseases (HDs) (autosomal dominant (AD), autosomal recessive (AR), and X-linked diseases) has been studied in five districts of Bashkortostan Republic: Burzyanskii, Abzelilovskii, Baimak, Salavatskii, and Arkhangel’skoe raions. The spectrum of HDs comprised 144 diseases, including 83, 48, and 13 AD, AR, and X-linked diseases. Most of them were found earlier during studies in ten other regions of Russia (Kirov, Kostroma, Tver’, Bryansk, and Rostov oblasts, and Krasnodar krai, and the republics of Adygea, Marii El, Udmurtia, and Chuvashia). Foci of local accumulation of some AD, AR, and X-linked diseases have been found in individual districts. Data on the gene frequencies for the HDs have been used for cluster analysis, which has shown the gene geographic position of Bashkirs among nine ethnic populations of Russia: Russians (Kostroma, Kirov, and Rostov oblasts and Krasnodar krai), Chuvashes (Chuvashia), Adygeans (Adygea), Maris (Marii El), Udmurts (Udmurtia), and Bashkirs (Bashkortostan).     

High-Speed Cell Sorting of Infectious Trophic and Cystic Forms of Pneumocystis carinii

ABSTRACT. The separation of Pneumocystis carinii life-cycle stages while preserving infectivity is a hitherto unresolved challenge. We describe an original, reproducible, and efficient method for separating trophic from cystic forms of P. carinii using a high-speed cell sorter. The large amounts of highly purified (99.6±0.3%) infectious trophic and cystic forms can now be used to elucidate the poorly understood P. carinii life cycle.     

Open Access to essential health care information

Open Access publishing is a valuable resource for the synthesis and distribution of essential health care information. This article discusses the potential benefits of Open Access, specifically in terms of Low and Middle Income (LAMI) countries in which there is currently a lack of informed health care providers - mainly a consequence of poor availability to information. We propose that without copyright restrictions, Open Access facilitates distribution of the most relevant research and health care information. Furthermore, we suggest that the technology and infrastructure that has been put in place for Open Access could be used to publish download-able manuals, guides or basic handbooks created by healthcare providers in LAMI countries.     

Nozological spectrum of hereditary diseases of the nervous system in the cities of Volgograd and Volzhsky

A spectrum of hereditary diseases of the nervous system (HDNS) was studied in the cities of Volgograd and Volzhsky. The estimates were obtained for the prevalence of major HDNS groups and individual nosological forms. The populations examined differed in prevalence of this pathology and in contribution of individual diseases and their nosological forms into HDNS load formation. The effect of the population dynamics in Volgograd and Volzhsky on the HDNS prevalence is discussed.     

Histology of Callogenesis and Somatic Embryogenesis Induced in Stem Fragments of Cork Oak (Quercus suber) Cultured In Vitro

Calluses able to produce somatic embryos were formed duringin vitro culture of shoot fragments of cork oak (Quercus suberL.).Histological monitoring of these fragments during cultureshowed that it was the cortical parenchyma cells which underwentdedifferentiation before calluses were formed by repeated divisions.The calluses consisted of parenchyma cells surrounded by a fewlayers of meristematic cells. Proembryos formed in groups aroundthe edge of some calluses. Histological examination showed thatthey were produced by the evolution of two different categoriesof cell: one category had the appearance of ‘embryogenic’cells with very thick walls, a small vacuole rich in starchand a well-developed nucleus with a prominent nucleolus. Theother cells were very bulky with large vacuoles; their morphologywas similar to that of suspensor cells encountered in embryogenesisin gymnosperms. The ontogenic stages were similar to those describedin zygotic embryos of the genus Quercus. Nevertheless, mostof the embryonic structures deviated from normal developmentand at all stages produced secondary proembryos. Cork-oak, Quercus suber L, histology, callogenesis, somatic embryogenesis, embryogenic cells, starch, secondary embryogenesis