Next generation sequencing panel as an effective approach to genetic testing in patients with a highly variable phenotype of neuromuscular disorders.

Neuromuscular disorders (NMDs) include a wide range of diseases affecting the peripheral nervous system. The genetic diagnoses are increasingly obtained with using the next generation sequencing (NGS). We applied the custom-design targeted NGS panel including 89 genes, together with genotyping and multiplex ligation-dependent probe amplification (MLPA) to identify a genetic spectrum of NMDs in 52 Polish patients. As a result, the genetic diagnosis was determined by NGS panel in 29 patients so its diagnostic utility is estimated at 55.8%. The most pathogenic variants were found in CLCN1, followed by CAPN3, SCN4A, and SGCA genes. Genotyping of myotonic dystrophy type 1 and 2 (DM1 and DM2) as a secondary approach has been performed. The co-occurrence of CAPN3 and CNBP mutations in one patient as well as DYSF and CNBP mutations in another suggests possibly more complex inheritance as well as expression of a phenotype. In 7 individuals with single nucleotide variant found in NGS testing, the MLPA of the CAPN3 gene was performed detecting the deletion encompassing exons 2-8 in the CAPN3 gene in one patient, confirming recessive limb-girdle muscular dystrophy type 1 (LGMDR1). Thirty patients obtained a genetic diagnosis (57.7%) after using NGS testing, genotyping and MLPA analysis. The study allowed for the identification of 27 known and 4 novel pathogenic/likely pathogenic variants and variants of uncertain significance (VUS) associated with NMDs.In conclusion, the diagnostic approach with diverse molecular techniques enables to broaden the mutational spectrum and maximizes the diagnostic yield. Furthermore, the co-occurrence of DM2 and LGMD has been detected in 2 individuals.

Alterations in transcranial sonography among Huntington's disease patients with psychiatric symptoms.

Transcranial sonography (TCS) is a diagnostic tool in mood and movement disorders. Alterations within the raphe mesencephalic nucleus in the brain have been reported not only in patients with major depression but in patients with depressive symptoms accompanying several neurodegenerative disorders. The aim of the study was to assess the echogenicity of the nucleus raphe and other basal ganglia in patients with Huntington's disease (HD). TCS was performed in 127 HD patients participating in observational studies (Registry/Enroll-HD) in the Institute of Psychiatry and Neurology (Warsaw, Poland). Raphe hypoechogenicity was found in 78% of HD patients with current symptoms of depression (according to DSM-IV criteria), 57% of patients with a previous history of depression, and 56.8% patients who lacked signs or history of depression. Patients with hypoechogenic raphe reported significantly higher depression as measured on the BDI (15.6 ± 1.7) as compared to patients with normal echogenicity (9.5 ± 1.2), (p = 0.023). The diameter of the third ventricle was negatively correlated with Mini-Mental State Examination (MMSE) (rho - 0.37) and total functional capacity (TFC) scores (rho - 0.26). Hyperechogenic substantia nigra was visualized in 66,4% patients with HD and the degree of hyperechogenicity was correlated with the total motor score (TMS) (rho - 0.38). Changes in echogenicity of the basal ganglia are related to both depressive and motor symptoms among patients with HD.

Next-generation sequencing study reveals the broader variant spectrum of hereditary spastic paraplegia and related phenotypes.

Hereditary spastic paraplegias (HSPs) are clinically and genetically heterogeneous neurodegenerative disorders. Numerous genes linked to HSPs, overlapping phenotypes between HSP subtypes and other neurodegenerative disorders and the HSPs' dual mode of inheritance (both dominant and recessive) make the genetic diagnosis of HSPs complex and difficult. Out of the original HSP cohort comprising 306 index cases (familial and isolated) who had been tested according to "traditional workflow/guidelines" by Multiplex Ligation-dependent Probe Amplification (MLPA) and Sanger sequencing, 30 unrelated patients (all familial cases) with unsolved genetic diagnoses were tested using next-generation sequencing (NGS). One hundred thirty-two genes associated with spastic paraplegias, hereditary ataxias and related movement disorders were analysed using the Illumina TruSight™ One Sequencing Panel. The targeted NGS data showed pathogenic variants, likely pathogenic variants and those of uncertain significance (VUS) in the following genes: SPAST (spastin, SPG4), ATL1 (atlastin 1, SPG3), WASHC5 (SPG8), KIF5A (SPG10), KIF1A (SPG30), SPG11 (spatacsin), CYP27A1, SETX and ITPR1. Out of the nine genes mentioned above, three have not been directly associated with the HSP phenotype to date. Considering the phenotypic overlap and joint cellular pathways of the HSP, spinocerebellar ataxia (SCA) and amyotrophic lateral sclerosis (ALS) genes, our findings provide further evidence that common genetic testing may improve the diagnostics of movement disorders with a spectrum of ataxia-spasticity signs.

Genetic polymorphisms and serum concentrations of adiponectin and resistin in anorexia nervosa and healthy controls - pilot study.

BACKGROUND: A possible role of adipokines in the regulation of body weight in patients with anorexia nervosa (AN) has been proposed. Polymorphisms in genes encoding adiponectin and resistin in AN have not been widely assessed, yet. OBJECTIVES: 1) Assessment the frequency of ADIPOQ c.45T>G, ADIPOQ c.276G>T polymorphisms in adiponectin and RETN c.62G>A, RETN c.-180C>G in resistin genes in AN patients and control group (C) 2) Analysis of correlation between these polymorphisms and serum ADP or RETN. METHODS: We examined 67 AN girls and 38 C aged 11-18. Analyses of polymorphisms in ADIPOQ and RETN genes were performed using RFLP method and adiponectin and resistin serum levels - with commercially available ELISA kits. RESULTS: In AN subjects, TT genotype in ADIPOQ c.276 polymorphism as well as GG genotype of RETN c.-180 were significantly more frequent than in CG. In ADIPOQ c.45 polymorphic site, TT alleles were the most frequent in both examined groups. In RETN c.62 GA and GG alleles distribution did not differ between the groups and the most frequently observed genotype was GG. The mean serum adiponectin level in AN was significantly higher and resistin - lower than in controls. There were no statistically significant relationships between serum adiponectin and resistin levels and allele frequency in polymorphisms ADIPOQ c.276 as well as RETN c.-180 in the examined groups. CONCLUSION: Differences in genotype frequencies of ADIPOQ c.276 and RETN c.-180 suggest a need for studies on a larger cohort of patients with AN.

Chemerin serum levels in girls with anorexia nervosa.

BACKGROUND: The regulatory function of chemerin (CHEM) in the process of adipogenesis and the metabolism of adipocytes has been confirmed. Data from several studies have shown higher serum CHEM in obesity. To date, there are no available studies on serum CHEM concentrations in patients with anorexia nervosa (AN), which is recognized as a good biological model of the chronic atrophy of adipose tissue and energy metabolism disorders in humans. OBJECTIVES: The aim of the study was to assess serum CHEM concentrations in girls with AN in comparison to healthy and obese subjects and determine its relationship with body mass, BMI and insulin. METHODS: CHEM serum concentrations were evaluated using commercially available ELISA kit in 65 Polish girls with restrictive AN, in 39 healthy controls (H) and 64 girls with simple obesity (OB). RESULTS: The mean serum CHEM concentration in the AN group was significantly lower than in the H and OB groups. After adjusting for BMI, CHEM concentrations in the AN group were significantly lower than in the H group, but statistically higher than in the OB group. Significant correlations between serum CHEM and body mass (r=0.77), BMI (r=0.82), Cole index (r=0.81) and serum insulin (r=0.78) were observed.

[Increased nuchal translucency in chromosomally normal fetuses and pregnancy outcomes--a retrospective study]. / Przeziernosc karku powyzej 3,5 mm u plodów z prawidlowym karfiotypem--analiza wyników ciaz.

OBJECTIVES: The objective was to study the outcomes of fetuses with increased nuchal translucency > or = 3.5 mm and normal karyotype. MATERIALS AND METHODS: We performed a retrospective study on pregnancy outcomes and children development in 87 women with increased fetal nuchal translucency and normal karyotype who underwent chorionic villus sampling at our department. Mean observation period was 12 months after birth. Adverse pregnancy outcome was defined as miscarriage and intrauterine fetal demise, termination of pregnancy structural defect, neonatal death, genetic syndrome and other major abnormalities. RESULTS: The total incidence of adverse pregnancy outcome was 39.1% (n = 34). The likelihood of an adverse pregnancy outcome, a major structural defect or major heart defect increased significantly with nuchal translucency (OR 3.77). 68 children (78.2%) were born alive. Nuchal translucency was significantly higher in newborns with adverse pregnancy outcome than in healthy children [4.1 mm vs. 5.7 mm; p < 0.01]. After a normal anomaly scan at 20 weeks gestation the risk of adverse outcome was 14.5% (n = 9, 9/62) and increased with nuchal translucency thickness from 10.2% for NT 3.5-4.4 mm to 100% for NT > or = 6.5 mm [p < 0. 0 1]. There was no significant relationship of fetal gender maternal age and persistence of the nuchal fold with adverse pregnancy outcome. The rate of neurodevelopmental delay was 3.4 % and was not higher than in the general population. CONCLUSIONS: The overall risk of adverse pregnancy outcome was around 40% and was related to nuchal translucency thickness. After excluding structural defects, the chance of a favorable outcome was 85%. The rate of neurodevelopmental delay in fetuses with increased nuchal translucency normal karyotype and normal anatomy is not higher than in the general population.

Self-assessment and self-perception of the body in 18-year-old girls.

INTRODUCTION: Studies focusing on self-perception of one's body usually cover subjects with eating disorders. There is a lack of similar studies. AIM OF THE STUDY: Conducting survey research on self-assessment and self-perception of one's own body in girls. MATERIAL AND METHODS: A survey was conducted in 1047 female students (average age: 18 years ±0.25) focusing on self-assessment and self-perception of their body mass, body parts, and eating habits. The study subjects were divided into groups of normal weight, obese, and underweight according to their BMI and BMI-SDS. RESULTS: There were twice as many girls dissatisfied with their body weight in the underweight group and 10 times as many in the obese group. 8% of girls with normal body weight perceived their body as overweight. 70% of subjects with a normal body weight and ca. 25% of obese thought they were obese in the area of the abdomen, hips, buttocks, and thighs. Fear of gaining weight was characteristic most often for girls with abnormal body weight who confessed to eating disorders. CONCLUSIONS: 1. Most 18-year-old girls do not demonstrate any symptoms of distorted body self-perception; a vast majority of girls with normal body weight exaggerate the shapes of body parts, which causes them to undertake measures aiming to lose weight. Only a quarter of obese subjects perceive their individual body parts as obese, which might result in their lack of motivation to lose weight. 2. It is necessary to introduce healthy lifestyle educators in schools to prevent ED and obesity in adolescents.

Assessment of Long-Term Treatment Results in Women Suffering from Anorexia Nervosa in Adolescence.

INTRODUCTION: Reports assessing long-term treatment outcomes for anorexia nervosa (AN) are divergent and refer to different populations. They lack long-term observations in AN patients in Poland. AIM OF THE STUDY: Analysis of the recovery, relapse rate, and predictive factors in patients treated due to AN in adolescence. MATERIAL AND METHODS: A total of 201 subjects were given a survey. Ninety-seven women were recruited: 56 reported to the clinic and 41 filled in the survey. RESULTS: The average period from hospitalization to the survey was 7.76 ±4.39 years. Remission was found in 78.4%, 21.6% still pre-sented AN, and 84.2% required a one-off hospitalisation, 10.5% twice. The average BMI was: 20.08 ±3.24 kg/m 2 . The rate of attempted suicides was 6.2%. Predictive factors for poor outcome were as follows: older age of the patient when falling ill, lower SDS-BMI score at the onset of AN, transition from the restrictive type of AN into a binge-eating/purging type, and fail-ure to maintain contact with the mother. CONCLUSIONS: 1. Most girls suffering from the restricting type of AN in adolescence are cured permanently. 2. The severity of symptoms in these girls does not eliminate the chance of recovery and achieving important life goals, com-pleting education, finding a life partner, and having children. 3. Girls with a smaller degree of cachexia at onset of AN, with no binge-eating/purging symptoms, maintaining regular con-tact with their mothers, have a better prognosis for recovery. 4. Six per cent of women treated in their youth for AN face the risk of attempted suicide, which points to the need to monitor their mental state for many years.

Assessment of the frequency of hormonal disorders of the gonads and bone mineral density among women treated for anorexia nervosa in adolescence.

INTRODUCTION: There are very few studies evaluating the activity of gonads in women treated for anorexia nervosa (AN) in adolescence, and reports on the bone mineral density in such patients are divergent. Objective Assessment of the incidence of gonadal hormonal function disorders and reduction of bone mineral density in women treated for AN in adolescence. MATERIAL AND METHODS: Out of 97 women who had participated in a survey study, 56 reported personally to the clinic. Their somatic condition, body weight, and BMI were evaluated, as well as levels of oestradiol, LH, FSH in blood serum were determined and DEXA scans were performed. RESULTS: The average period of hospitalisation until the time of the study was 7.08 ±4.47 years. BMI was as follows: 20.01 ±3.6 kg/m2. 25% women were still sick, 75% were considered cured. In 17.9% of the study subjects hypogonadotropic hy-pogonadism was diagnosed. Abnormal results of the densitometric scan were confirmed in 85.7% of the study subjects. In the group of women with normal body weight only 19% had normal levels of bone mineral density. CONCLUSIONS: 1. In almost 18% of women treated for AN in adolescence, disorders of the hormonal function of gonads persist, despite normal body weight in 50% of them. 2. Bone mineral density is reduced in most women treated for AN, which indicates the need to monitor the condition of the bones, an early introduction of prevention of osteopenia and osteoporosis since the onset of AN in order to prevent bone fractures in adulthood.

Application of a custom NGS gene panel revealed a high diagnostic utility for molecular testing of hereditary ataxias.

Hereditary ataxias (HA) are a rare group of heterogeneous disorders. Here, we present the results of molecular testing of a group of ataxia patients using a custom-designed next-generation sequencing (NGS) panel. Due to the genetic and clinical overlapping of hereditary ataxias and spastic paraplegias (HSP), the panel encompasses together HA and HSP genes. The NGS libraries, comprising coding sequences for 152 genes, were performed using KAPA HyperPlus and HyperCap Target Enrichment Kit, sequenced on the MiSeq instrument. The results were analyzed using the BaseSpace Variant Interpreter and Integrative Genomics Viewer. All pathogenic and likely pathogenic variants were confirmed using Sanger sequencing. A total of 29 patients with hereditary ataxias were enrolled in the NGS testing, and 16 patients had a confirmed molecular diagnosis with diagnostic accuracy rate of 55.2%. Pathogenic or likely pathogenic mutations were identified in 10 different genes: POLG (PEOA1, n = 3; SCAE, n = 2), CACNA1A (EA2, n = 2), SACS (ARSACS, n = 2), SLC33A1 (SPG42, n = 2), STUB1 (SCA48, n = 1), SPTBN2 (SCA5, n = 1), TGM6 (SCA35, n = 1), SETX (AOA2, n = 1), ANO10 (SCAR10, n = 1), and SPAST (SPG4, n = 1). We demonstrated that an approach based on the targeted use of the NGS panel can be highly effective and a useful tool in the molecular diagnosis of ataxia patients. Furthermore, we highlight the fact that a sequencing panel targeting both ataxias and HSP genes increases the diagnostic success level.

Assessment of serum levels resistin in girls with anorexia nervosa. Part II. Relationships between serum levels of resistin and thyroid, adrenal and gonadal hormones.

OBJECTIVES: Thyroid, adrenal glands and gonadal hormones play a role in maintaining metabolic homeostasis of the body via the receptors located in the adipose tissue. The correlations between serum resistin (RES) and function of other hormonal axes in patients with AN have not been established, yet. Therefore, the aim of this study is: 1) assessment of concentrations of thyroid hormones (FT4, TSH), adrenal hormones (ACTH, cortisol), sex hormones (LH, FSH, estradiol, testosterone); 2) establishing their relationship with BMI and 3) analysis of correlations between examined hormones and RES serum concentrations in adolescent female patients with AN. DESIGN AND SETTING: Serum RES (ELISA) and fT4, TSH, ACTH, LH, FSH, estradiol and testosterone (ECLIA) concentrations have been assayed in 195 adolescent girls: 87 with restrictive AN, 17 with not otherwise specified eating disorders (NOS), 30 with simple obesity (OB) and 61 healthy (H) subjects. RESULTS: Mean serum FT4, LH and estradiol concentrations were significantly lower (p=0.015; p<0.0001; p<0.0001, respectively) in AN than in OB group, and cortisol increased (p<0.001) compared to OB and H subjects. In all examined subjects BMI correlated positively (p<0.0001) with LH (r=0.61) and estradiol (r=0.30), and negatively with cortisol (r=-0.35; p=0.008). Also the significant positive relationship between serum RES and FT4 (r=0.34), LH (r=0.57) as well as estradiol (r=0.28) was observed, whereas serum cortisol correlated negatively with RES (r=-0.40). CONCLUSION: Changes in resistin serum concentrations in eating disorders may be involved in the altered regulation of hypothalamic-pituitary-adrenal, thyroid and gonadal axes.

Assessment of serum levels resistin in girls with anorexia nervosa. Part I. Relationship between resistin and body mass index.

OBJECTIVES: There are only few studies available on blood resistin (RES) levels in patients with anorexia nervosa (AN), which revealed scarce results, however it has been demonstrated that RES mRNA expression in adipose tissue of these patients is increased. The aim of this study is: 1) the evaluation of serum resistin levels in girls with AN and determination a threshold value differentiating these patients from healthy subjects; 2) analysis of the relationship between serum resistin levels and BMI in examined subjects. DESIGN AND SETTING: Serum RES concentration has been assayed using ELISA kit in 195 adolescent girls: 87 with restrictive AN (mean BMI-SDS: -2.65 ± 0.2), 17 with not otherwise specified eating disorders (NOS) (mean BMI-SDS: -1.4 ± 0.68), 30 with simple obesity (OB) (mean BMI-SDS: 6.91 ± 1.23) and 61 healthy (mean BMI-SDS: -0.18 ± 0.54). RESULTS: Mean serum RES concentration in AN (2.8 ± 0.6 ng/ml) and NOS (3.1 ± 0.9 ng/ml) were significantly lower (p<0.0001) than in OB and H groups (4.8 ± 0.5 and 4.1 ± 0.4 ng/ml respectively). After corrected for BMI, RES values in AN were similar as in H subjects, but significantly higher (p<0.005) in comparison to OB group. ROC curve analysis revealed that 3.87 ng/ml is the threshold value of RES serum concentration differentiating AN from H girls (specificity 100%, sensitivity 80%). No significant correlations between BMI and serum resistin concentration are found in AN group, although a significant positive correlation has been established for all examined subjects. CONCLUSION: Additional adaptive mechanisms may be involved in regulation of RES levels in adolescent girls with AN.

Evaluation of the frequency of ADIPOQ c.45 T>G and ADIPOQ c.276 G>T polymorphisms in adiponectin coding gene in girls with anorexia nervosa.

INTRODUCTION: Anorexia nervosa (AN) is a serious chronic psychosomatic disorder, the essence of which are attempts by the sufferer to obtain a slim silhouette by deliberate weight loss (restrictive diet, strenuous physical exercise, provoking vomiting). The aetiology of this disorder is multifactorial. Genetic factors that influence the predisposition to AN have been sought. A broad meta-analysis points to a strong genetic correlation between AN and insulin resistance. Adiponectin (ADIPO) increases insulin sensitivity. In our pilot study we demonstrated that the TT genotype in locus ADIPOQ c.276 G>T of the ADIPO gene and a higher concentration of ADIPO in blood serum occurred significantly more frequently in 68 girls suffering from AN than in 38 healthy girls. The objective of this study was to evaluate the frequency of the occurrence of ADIPOQ c.45 T>G and ADIPOQ c.276 G>T in the ADIPO gene in a larger cohort of girls with AN and healthy girls, as well as an analysis of correlations between variants of the aforementioned polymorphisms and the levels of ADIPO in blood serum. MATERIAL AND METHODS: The study covered 472 girls (age: 11-19 years): 308 with the restrictive form of AN (AN) and 164 healthy girls (C). The level of ADIPO in blood serum was determined by means of the ELISA method on a Bio-Vendor, LLC (Asheville, North Carolina, USA). The DNA isolation was carried out by means of Genomic Mini AX BLOOD (SPIN). The PCR reaction was carried out in a ThermoCycle T100 thermocycler. 80-150 ng of the studied DNA and relevant F and R starters were added to the reaction mixture. The reaction products were subjected to digestion by restriction enzymes and separated on agarose gels (RFLP). RESULTS: The distribution of genotypes in the polymorphic site ADP c.45 of the ADIPO gene and ADP c.276 was similar in both groups. In both groups the T allele was most frequent in locus ADIPOQ c.45 and the G allele in locus ADIPOQ c.276. In all the study subjects collectively (AN and C) a statistically significant negative correlation between the levels of ADIPO in blood serum on one hand and body weight (r = -0.46; p < 0.0001) and BMI (r = -0.67; p < 0.0001) on the other was demonstrated. Exclusively in the AN group a significant correlation between the level of ADIPO in blood and the distribution of TG, TT, and GG alleles in loci ADIPOQ c.45 and ADIPOQ c.276 was demonstrated (p = 0.0052 and p < 0.0001, respectively). CONCLUSIONS: The genotype in loci ADIPOQ c.45 and ADIPOQ c.276 of the ADIPO gene seems to have no effect on the predisposition to AN. Girls suffering from AN with the TT genotype in loci ADIPOQ c.45 and ADIPOQ c. 276 may demonstrate higher insulin sensitivity because they have significantly higher levels of ADIPO than girls suffering from AN with other genotypes. This may be suggestive of their better adaptation to the state of malnutrition, and it has a potential effect on treatment results.

Evaluation of the frequency of RETN c.62G>A and RETN c.-180C>G polymorphisms in the resistin coding gene in girls with anorexia nervosa.

INTRODUCTION: Anorexia nervosa (AN) is a serious psychosomatic syndrome, classified as an eating disorder. AN patients strive to lose weight below the normal limits defined for a specific age and height, achieving their goal even at the expense of extreme emaciation. AN has a multifactorial aetiology. Genetic factors are believed to be significant in the predisposition to the development of AN. In girls suffering from AN significantly lower levels of resistin (RES) in blood serum are observed as compared to healthy girls. These differences may lead to a thesis that functional genetic polymorphisms in RES coding genes can be responsible for this phenomenon. In our pilot study we demonstrated significant differences in the distribution of genotypes in the locus RETN c.-180C>G of the RES gene in 67 girls with AN and 38 healthy girls. It seems reasonable to compare the frequency of polymorphisms of RETN c.62G>A and RETN c.-180C>G in the RES gene in girls with AN and in healthy subjects in a bigger cohort and to analyse correlations between individual variants of the polymorphisms referred to above and the RES levels in blood plasma. MATERIAL AND METHODS: The study covered 308 girls with the restrictive form of AN (AN) and 164 healthy girls (C) (aged 11-19 years). The RES levels in blood serum were determined by means of the ELISA method on a Bio-Vendor machine from LLC (Asheville, North Carolina, USA). The DNA isolation was carried out by means of Genomic Mini AX BLOOD (SPIN). The PCR reaction was carried out on a ThermoCycle T100 thermocycler. 80-150 ng of the studied DNA and relevant F and R starters were added to the reaction mixture. The reaction products were subjected to digestion by restriction enzymes and separated on agarose gels (RFLP). RESULTS: The average RES level in blood serum in the AN group was significantly lower (p < 0.0001) than in the C group. The distribution of genotypes in the locus RETN c.62 of the RES gene was similar in both groups. A significant difference was demonstrated in the distribution of genotypes in the polymorphic site RETN c.-180 of the RES gene between AN and C (p = 0.0145) and in the distribution of the C and G alleles in the locus RETN c.-180 (p < 0.0001). The C allele occurred significantly more frequently than the G allele in the C group as compared to the AN group. In all the study subjects jointly (AN and C) a significant positive correlation between the blood RES levels on one hand and the body mass (r = 0.42; p < 0.0001) and BMI (r = 0.61; p< 0.0001) on the other was observed. There was no correlation between the concentration of RES in blood serum and the distribution of genotypes in the loci of the resistin gene referred to above. CONCLUSIONS: The CG genotype in the locus RETN c.-180 C>G of the RES gene may constitute one of the factors predisposing to the development of AN in girls. The genotype in the loci RETN c.62 G>A and RETN c.-180 C>G of the resistin gene has no influence on the levels of this hormone in blood in AN patients.

Trends of underweight and obesity prevalence among adolescent girls in the selected population of the Silesian Agglomeration.

OBJECTIVE OF THE STUDY: 1. Determination of the state of nutrition in the examined population of 18-year-old girls. 2. Retrospective determination of the state of nutrition of the same girls when they were 14 years old. 3. The answer to the question whether the examined group exhibits the tendency to consolidate abnormalities in terms of the body weight over time. MATERIAL AND METHODS: 1047 female students of secondary schools, aged 18, were subjected to anthropometric measurements (body weight, height, BMI, BMI-SDS) and took part in a survey questionnaire devoted to their eating habits. The measurement results of the same girls aged 14 were obtained retrospectively. RESULTS: When the subjects were 14 years old, 79.7% of them had a normal body weight, 14.9% were obese, and 5.4% were underweight. At the age of 18, 76.6% of the subjects had a normal body weight, 17.2% were obese, and 6.2% were underweight. 4.7% of the girls with a normal weight aged 14 reduced their body weight, and 9.2% became obese at 18 the age of 18. None of the underweight subjects demonstrated obesity at the age of 18, and 45.6% maintained their body weight below the normal limits. 66% of the girls who were obese at the age of 14 maintained their obesity at the age of 18. CONCLUSIONS: 1. Most girls in the examined population at 14 and 18 years of age demonstrate a normal nutrition state. Obesity was observed in 15% of the examined females at the age of 14 and in 17% at the age of 18, whereas 5% of girls aged 14 and 6% of girls aged 18 are underweight. 2. From early to late adolescence a tendency to persistent abnormalities of the nutritional status is observed in girls. 3. Obesity in girls aged 14 is a predictor for obesity at the age of 18 and perhaps in the adult life.

A rare subclinical or mild type of Becker muscular dystrophy caused by a single exon 48 deletion of the dystrophin gene.

In the material of 227 families with Becker muscular dystrophy (BMD), we found nine non-consanguineous families with 17 male individuals carrying a rare mutation-a single exon 48 deletion of the dystrophin gene-who were affected with a very mild or subclinical form of BMD. They were usually detected thanks to accidental findings of elevated serum creatine phosphokinase (sCPK). A thorough clinical analysis of the carriers, both children (12) and adults (5), revealed in some of them muscle hypotonia (10/17) and/or very mild muscle weakness (9/17), as well as decreased tendon reflexes (6/17). Adults, apart from very mild muscle weakness and calf hypertrophy in some, had no significant abnormalities on neurological assessments and had good exercise tolerance. Parents of the children carriers of the exon 48 deletion are usually unaware of their children being affected, and possibly at risk of developing life-threatening cardiomyopathy. The same concerns the adult male carriers. Therefore, the authors postulate undertaking preventive measures such as cascade screening of the relatives of the probands. Newborn screening programmes of Duchenne muscular dystrophy (DMD)/BMD based on sCPK marked increase may be considered.

Serum vaspin concentrations in girls with anorexia nervosa.

BACKGROUND: Vaspin (VASP) is a protein detected in pre- and mature adipocytes, the production and secretion of which may be conditioned by nutrition status. VASP may also play a role in the regulation of food intake. Since to date, there are no available studies on serum vaspin concentrations in patients with anorexia nervosa (AN), the aim of our study is to assess serum vaspin concentrations in girls with AN in comparison to healthy subjects and determine its relationship with body weight, body masss index (BMI) and insulin. METHODS: In this cross-sectional study vaspin serum concentrations were evaluated using a commercially available ELISA kit in 47 Polish girls hospitalized due to restrictive AN and 39 healthy controls (H). RESULTS: The mean serum concentration of VASP in girls with AN was significantly higher than in the H group. These differences were also noted after adjustment for body masss index-standard deviation score (BMI-SDS), the homeostatic model assessment-insulin resistance (HOMA-IR) index and insulin levels. There were no statistically significant correlations between the serum concentrations of VASP and body mass, BMI, BMI-SDS, insulin and HOMA-IR in the AN or healthy group. CONCLUSIONS: Serum vaspin levels in lean subjects are regulated in different mechanisms than previously reported in obesity. It should be established if elevated serum vaspin levels in girls with AN may contribute to low food intake in these patients.

Familial cerebral cavernous malformation.

Cavernous malformations (CMs) occur in approximately 0.5% of the general population and represent 5-10% of the central nervous system vascular malformations. The majority of CMs appear sporadically but genetically determined familial forms account for 10% to 15% of all cases. The aim of this study was to discuss the clinical, pathological and genetic aspects of familial cerebral cavernous malformations (CCMs). We report on five members of a family who underwent surgery due to CCMs. However, only two members were treated in our Department. The age of onset of symptoms in these cases (4 men and 1 women) ranged from 3 to 28 years. Three members of the family were asymptomatic but it turned out that they were obligatory gene carriers and in one of them the cavernous malformation was confirmed by neuroimaging study. The clinical symptoms of CCMs included seizure (three patients) and focal neurological deficit (two patients). Multiple CCMs were identified in two symptomatic patients (two lesions) and in one asymptomatic patient (three lesions). The lesions were located superficially (4), in the basal ganglia (1), in the brainstem (2) and in the cerebellar vermis (1). In two patients, the subsequent imaging studies showed a single de novo CCM formation. Only one patient with mutation of CCM2 gene was treated surgically. In patients with cavernous malformations the detailed clinical and family history of neurological events ought to be collected. This is particular important in patients with multiple changes or with de novo CCMs formation, identified in subsequent imaging studies. A well-documented family history can help to establish the final diagnosis and makes it possible to offer all members of the family proper neurological and genetic care.