Description of a large cohort of Caucasian patients with V122I ATTRv amyloidosis: Neurological and cardiological features.

V122I is one of more than 130 mutations in transthyretin gene associated with hereditary TTR (ATTRv) amyloidosis. Main clinical expression is an infiltrative pseudohypertrophic cardiomyopathy with mild or no neurological symptoms. It is particularly common among African-Americans (prevalence: 3%-4%). We report 12 subjects from seven unrelated Caucasian families hailing from Sicily and carrying the V122I mutation. One patient was homozygous for V122I and in another family two subjects also carried the E89Q variant in compound heterozygosity. All the subjects underwent neurologic/neurophysiologic evaluation and cardiologic baseline tests; in five of them, cardiac magnetic resonance and/or (99 m) Tc-DPD scintigraphy were performed. Three of 12 subjects were asymptomatic carriers. Of the remaining nine subjects, in four of nine patients, the nerve conduction studies revealed a polyneuropathy; in one of them, this represents the only sign of disease after 5 years of follow-up. In eight of nine subjects, we found a hypertrophic restrictive cardiomyopathy and cardiac failure, associated with a carpal tunnel syndrome. Although in non-Afro-American individuals V122I prevalence is low, subjects carrying this mutation have been identified in the United Kingdom, Italy, and France. Our report describes a large cohort of V122I Caucasian patients from a non-endemic area, confirming the possible underestimation of this mutation in the non-African population. Moreover, it highlights the heterogeneity in the genotype-phenotype correlation of ATTRv mutations, suggesting that the presence of a polyneuropathy has to be identified as soon as possible, since available treatments are, in Europe, so far authorized only for ATTRv amyloid peripheral neuropathy.

Prevalence and Incidence of Multiple Sclerosis in the City of Biancavilla.

BACKGROUND: It is common that the epidemiology of multiple sclerosis (MS) varies with geography and ethnicity. Recent studies show a continuous growth of incidence and prevalence in Sicily, despite the controversial "latitude gradient theory." OBJECTIVES: The aim of our study is to ascertain incidence and prevalence rates of MS in the city of Biancavilla, Sicily, Southern Italy. METHOD: Case ascertainment approach and a clinical database collecting data of MS cases to Biancavilla, according to McDonald 2011 and Thompson 2018 criteria, from 1992 to 2018, have been used to the study. We further collected information regarding the familiarity of patients with Mesothelioma, highly incident in this geographic area. RESULTS: The results showed an increase of the mean annual incidence for the period 2012-2018 (16.8/100,000) compared to 1992-1996 (4.5/100,000), and a standardized incidence ratio of 1.41 (95% CI 0.74-2.45). On December 31, 2018, 70 patients suffering from definite MS and living in Biancavilla yielded a crude prevalence of 292.3 per 100,000 (198.2/100,000 for men; 380.7/100,000 for women) with a standardized morbidity ratio of 2.3 (95% CI 1.8-2.9). CONCLUSIONS: Our data confirmed Biancavilla is an area at high risk for MS, ascribable to increased survival, improved ascertainment, or maybe related to a genetic or environmental risk. At the time, any relation with mesothelioma was excluded.

Perception of rubella risk in pregnancy: an epidemiological survey on a sample of pregnant women.

BACKGROUND: Rubella is a common exanthematous viral disease all over the world. The disease can be prevented by administering a safe and effective vaccine, and in Italy it is subject to reporting obligations. A national plan for the elimination of measles and congenital rubella (in Italian "PNEMoRC") was approved in 2003 and updated in 2010. This plan originally aimed at reducing the susceptible target population (women in fertile age, 15-49 years old) to below 5% and at eliminating the congenital form of rubella by 2015, a goal which has not been achieved yet. STUDY DESIGN: Our research work was focused on a convenience sample of pregnant women attending the antenatal classes at the two main hospitals in Messina, Sicily (Italy). METHODS: After we obtained an informed consent, we administered to 200 Italian and foreign pregnant women an anonymous questionnaire reporting socio-demographic characteristics, type of gynaecological assistance and information received about Rubella serological statu. RESULTS: The mean age was 30.6 years ± 5.45. The majority of these women were married, at work and with a high educational level. Most of them (75.3%) reported to be assisted by a private gynaecologist, while only 24.7% used a public facility. A remarkable percentage (62.8%) of these women reported to be serologically negative at the anti-rubella antibodies test, but, only 7.5% of them reported to have passed the anti-rubella antibody test before the conception. CONCLUSION: Our results clearly show that we are still far from achieving the elimination of rubella risk in pregnancy. We are facing a cultural gap perhaps also due to a generalized loss of "historical memory" about the impact that infectious diseases have had in the past in terms of mortality and morbidity. In fact, alongside the considerable drop in vaccination coverage in the recent years, our research also reveals a reduced focus on pre-conceptional testing and limited awareness of associated risks. Furthermore, we correlated the serological status with the sociodemographic characteristics of these women and found a statistically significant correlation with their age and their educational level (P<0.05). A lot still needs to be done to improve the situation; in particular, better education at various levels could considerably increase the awareness among women about this relevant public health issue.

Evaluation of HPFH and 뫧-thalassemia mutations in a Brazilian group with high Hb F levels.

Fetal hemoglobin (Hb F) is characteristic of the fetal development period. However, in some genetic conditions, such as hereditary persistence of fetal hemoglobin (HPFH) and delta-beta thalassemia (뫧-thalassemia), Hb F continues to be produced in adulthood. We evaluated the frequency of two mutations of HPFH, HPFH-1 and HPFH-2 African, and two mutations in 뫧-thalassemia, Sicilian and Spanish, in a Brazilian population. Peripheral blood samples were collected from adults from hospitals and blood centers in southeast and northeast Brazil. These individuals were healthy and without complaints of anemia, but had increased Hb F. Samples were submitted to electrophoretic and chromatographic analyses to quantify Hb F values and, subsequently, to molecular analyses to verify the mutations. In the molecular analysis, 16 of the 60 samples showed a heterozygous profile for the HPFH mutations, two for HPFH-1 and 14 for HPFH-2. In the same sample set, three were heterozygous for Spanish 뫧-thalassemia and none were heterozygous for Sicilian 뫧- thalassemia. The Hb F values in the HPFH-2 heterozygotes differed from those previously reported for this mutation. In this group, the HPFH mutations were more frequent than the 뫧-thalassemia mutations. The finding of these mutations in this Brazilian population reflects the mixing process that occurred during its formation.

Why does head form change in children of immigrants? A reappraisal.

OBJECTIVES: We test two specific hypotheses that explain the cranial changes Boas observed in Hebrews and Sicilians, namely that Hebrew change results from abandoning cradling of infants in America, while in Sicilians it results from impaired growth in America. METHODS: Boas's (1928) data were used to test these hypotheses. The role of cradling in cranial shape was examined by comparing cranial indices of U.S.-born and foreign children between 1.5 and 5 years of age. Age changes in cranial index of Hebrew and Sicilian children ages five to eighteen were examined to demonstrate differing patterns of age changes, which could be explained by environmental differences. Statistical methods employed were t-tests, least squares, and loess regression. RESULTS: The difference between American and foreign-born Hebrew children arose prior to five years of age, after which it remained constant. American and foreign-born Sicilians, on the other hand, had similar cranial indices at age five, and diverged during the growing years, primarily because American-born children did not exhibit the reduction in cranial index with age seen in the other groups. CONCLUSIONS: The results support the two hypotheses tested. Change in Hebrew cranial indices resulted from abandoning the practice of cradling infants in America. U.S.-born Sicilian children experienced an environment worse than the one in Europe, and consequently experienced impaired growth. We conclude that the changes Boas observed resulted from specific behavioral and economic conditions unique to each group, rather than a homogeneous American environment.

A journey into the imaginary of Sicilian pastry.

This article is an anthropological archeology of Sicilian confectionery, from the prehistoric-like assemblage of sesame seeds and honey (giurgiulena) to the extravagant gelato di campagna and the baroque-rustic cassata. Sweets are analyzed as architectural constructions that rely on newly discovered ingredients and techniques to create edible edifices that amazed the eye as much as the palate. They emerge from their historical and social context and affirm themselves as moments of innovation in the culinary art. On a deeper level, the art of pasticceri bears the marks of an existential quest that constantly redefines man's symbolic relation to the forces and contrasts of life.

Human leukocyte antigen frequency in human high-grade gliomas: a case-control study in Sicily.

OBJECTIVE: Human leukocyte antigens (HLAs) are widely expressed cell surface molecules that present antigenic peptides to T lymphocytes and modulate immune response against inflammatory and malignant diseases. The aim of this study was to compare HLA distribution in patients with newly diagnosed high-grade gliomas (HGGs) and 2 control groups from a restricted geographic area (eastern Sicily). METHODS: HLA allele frequency, as determined from peripheral blood of 56 adult patients with HGGs, was compared with that of 2 different control groups: 140 healthy bone marrow donors (group A) and 69 virtually brain tumor-free patients (group B). HLA expression was evaluated using a reverse transcriptase polymerase chain reaction-sequence-specific oligonucleotide probe. RESULTS: There was significant expression of HLA-A*11 in patients with HGGs compared with control groups A and B (P < 0.003 and P < 0.018, respectively). Significant expression of HLA genotypes in patients with HGGs was also identified for HLA-DQB1*06 (P = 0.005), HLA-DRB1*14 (P = 0.001), and HLA-DRB3*01 (P = 0.007) compared with control group B. In HGG patients, there was statistically significantly decreased expression, compared with control groups A and B, of HLA-B*07 (P = 0.002 and P = 0.03, respectively) and HLA-C*04 (P = 0.007 and P = 0.016, respectively). There was statistically significant lower expression of HLA-C*05 in the HGG group compared with group B (P < 0.03). CONCLUSION: This is the first study to describe the frequency of distribution of HLAs in a population from a restricted geographic area. The findings suggest a possible correlation between HLA allele distribution and the occurrence of newly diagnosed malignant astroglial brain tumors.

Is BRCA1-5083del19, identified in breast cancer patients of Sicilian origin, a Calabrian founder mutation?

Various studies have been published in Italy regarding the different BRCA1 mutations, but only the BRCA1-5083del19 mutation is recurrent and specific to individuals of Italian descent with a founder effect on the Calabrian population. In our previous study, BRCA1-5083del19 mutation carriers were found in four index cases of 106 Sicilian patients selected for familial and/or hereditary breast/ovarian cancers. The high frequency rate of this mutation identified in the Sicilian population led us to perform haplotype analysis in all family carriers. Five highly polymorphic microsatellite markers were used (D17S1320, D17S932, D17S1323, D17S1326, D17S1325) to establish whether or not all these families had a common ancestor. This analysis showed that all mutation carriers of these families had a common allele. None of the non-carriers of the mutation or of the 50 healthy Sicilian controls showed this haplotype. This allelotype analysis highlighted the presence of a common allele (ancestor), thus suggesting the presence of a founder effect in the Sicilian population. Our results are in contrast with other studies but only the allelotype analysis of all the BRCA1-5083del19 mutation carriers of two neighboring regions of the south of Italy (Calabria and Sicily) will make it possible to identify the real ancestor of this mutation.

In Sicilian ethnic group non-classical congenital adrenal hyperplasia is frequently associated with a very mild genotype.

The spectrum of mutated alleles in non-classical congenital adrenal hyperplasia (NC-CAH) has been recently reported to be very large and haplotypes may significantly differ in the different ethnic groups. In order to confirm that population differences may exist in the genetic basis of this disease, we have analyzed the genetic presentation of NC-CAH in a Sicilian cohort of symptomatic patients and compared our findings with the ones reported in other studies of different ethnic groups. In 38 NC-CAH patients coming from two regions of Sicily and born of Sicilian parents, we found that 84.2% of the chromosomes examined bore only mild mutations and only the remaining 15.8% of the chromosomes bore at least 1 severe mutation. The overall predominant mutation was V281L, which was detected in 73.7% of alleles and in 89.5% of patients. About 58% of the patients were homozygotes for this mutation. V281L allele and homozygote frequencies were higher in the present series than in other European and Italian reports. In our NC-CAH population, which is one of the largest ever reported, the patients with two mild mutations exhibited a less severe impairment of both clinical and endocrine phenotype. On the basis of these results we can conclude that: a) in Sicilian ethnic groups NC-CAH is frequently associated with a very mild genotype; b) the most frequent genotype in our series is V281L homozygosis; c) clinical and biochemical expression of NC-CAH is more marked in the patients bearing a severe mutation; d) no correlations between genotype and phenotype were found in our patients affected by NC-CAH.

Six novel mutations of the LDL receptor gene in FH kindred of Sicilian and Paraguayan descent.

Familial hypercholesterolemia (FH) is an autosomal dominant inherited disease caused by mutations in the gene coding for the low density lipoprotein receptor (LDL-R). It is characterized by a high concentration of low density lipoprotein (LDL), which frequently gives rise to premature coronary artery disease. We studied the probands of five FH Sicilian families with 'definite' FH and one proband of Paraguayan descent with homozygous FH who has been treated with an effective living-donor liver transplantation. In order to seek the molecular defect in these six families, we used direct sequencing to define the molecular defects of the LDL-R gene responsible for the disease. We described three novel missense mutations (C100Y, C183Y and G440C), two frameshift mutations (g.1162delC in exon 8 and g.2051delC in exon 14) and one mutation (g.2390-1Gright curved arrow A) at splicing acceptor consensus sequences located in intron 16 of the LDL-R gene; the analysis of cDNA of this splicing mutation showed the activation of a cryptic splice site in intron 16 and the binding studies showed a reduction in internalisation of LDL-DIL in the proband's cultured fibroblasts. Moreover, a g.2051delC in exon 14 was identified in the proband of Paraguayan ancestry with clinical features of homozygous FH. The mutation identified in the South American patient represents the first description of a variant in South American patients other than Brazilian FH patients. The 5 mutations identified in the Sicilian patients confirm the heterogeneity of LDL-R gene mutations in Sicily.

Symmetry of healthy adult feet: role of orthostatic footprint at computerized baropodometry and of digital formula.

Morphological aspects of orthostatic footprints (anterior heel, isthmus, posterior heel), using computerized baropodometry and of the digital formula were studied in 97 subjects (37 males, 60 females; median age: 20.9+/-1.56) at the Medical School of Palermo, Italy. The aim of this study was to contribute to our knowledge of the bilateral symmetry and asymmetry of the human feet in ethnically similar groups. We evaluated the length of the footprints (FL) and the widths of the anterior heel (AHW), isthmus (IW), and the posterior heel (PHW). Values were compared in the left and right feet of each subjects. The general morphology of the footprints was considered to determine bilateral correspondence or divergence. We also evaluated the digital formula to verify any bilateral correspondence. The linear measurements of the footprints did not show any particular bilateral conformity. The general morphology of the footprint showed bilateral correspondence in 76 subjects (78%): in 21 subjects (22%) it did not show any. Typological results of the bilateral orthostatic footprints showed normalfootprints in 54 subjects (55.5%): the isthmus included 1/3 to 2/3 of the AHW. Hollow footprints were found in 20 subjects (20.5%): the isthmus was less than 1/3 of the AHW. At clinical examination, using the digital formula, we found that Egyptian foot (1 degree > 2 degrees) was the most frequent (68%). The standard foot (1 degree = 2 degrees) and the Greek foot (1 degree < 2 degrees) were both present in 16% of the feet examined. Seventy-nine subjects (82%) presented bilaterally correspondent digital formulas: 1 degree > 2 degrees in 59 subjects (62%), 1 degree = 2 degrees in 9 subjects (9%), and 1 degree < 2 degrees in 11 (11%). While comparison of the bilateral linear measurements studied showed that there was primarily no bilateral correspondence, the morphological aspects of the footprints and of the digital formulas showed that bilateral correspondence was prevalent.

Mitochondrial DNA sequence analysis in Sicily.

This study reports data on the sequences of the first hypervariable segment of a sample of the Sicilian population from Alia (Palermo, Italy). The results show the presence of 32 different haplotypes in the 49 individuals examined. The average number of pairwise nucleotide differences was 4.04, i.e., 1.17% per nucleotide. The distribution of the nucleotide differences matches the theoretical distribution and indicates only one major episode of expansion that occurred between 20,732 and 59,691 years ago, between the Middle Paleolithic and Upper Paleolithic. Compared with the other populations, parameters of the Sicilian sample lie in an intermediate position between the eastern and western Mediterranean populations. This is due to numerous contacts that Sicily has had with the Mediterranean area since prehistoric times. At the same time, the singularity of some of the haplotypes present in the sample studied indicates the persistence of some characteristics caused by genetic drift and isolation that the population has endured in the course of its history.

From illness narratives to social commentary: a Pirandellian approach to "nerves".

The concept of "nerves" is an integral component of the language of distress found in a number of societies. Individuals, however, often extend its meaning well beyond the realm of suffering. In this article, I examine some Sicilian-Canadian uses of "nerves" from a Pirandellian perspective. This, I believe, gives us an insight into how people (1) make use of illness narratives to give meaning to their life experiences, and (2) attempt to influence the thought and behavior of significant others. In the process, I address the question how do we move away from anthropological definitions and explanations that tend to simplify or mask some of the rich complexities surrounding the meaning(s) of "folk" concepts?

Molecular analysis in glycogen storage disease 1 non-A: DHPLC detection of the highly prevalent exon 8 mutations of the G6PT1 gene in German patients.

We investigated the molecular basis of glycogen storage disease type 1 non-A (GSD1 non-A) in 21patients. In addition to 8 novel mutations within the G6PT1 gene (c.250T>A, c.580G>A, c.627C>T, c.653-4delAG, c. 844C>A, c.1071A>C, c.1268G>A, c.1348G>A), we found a remarkably high prevalence of exon 8 mutations in German patients. The c.1211-2delCT mutation and the c.1184G>T mutation accounted for 32% and 29% of mutant chromosomes, respectively, supporting the hypothesis of a Middle European origin of these two mutations. Together with less common mutations, 79% of German GSD1 non-A patients were either homozygous or heterozygous for an exon 8 mutation. In addition to direct sequencing, these exon8 mutations could be detected by mutation-specific methods such as the detection of heteroduplex formation on polyacrylamide gel electrophoresis or by the amplification of DNA segments by allele-specific oligonucleotides. Furthermore, the use of denaturating high performance liquid chromatography (DHPLC) allowed a 100% detection and discrimination of all exon 8 mutations. In conclusion from these results, we recommend the use of either conventional or DHPLC screening as the initial non-invasive and efficient diagnostic procedure in patients with GSD1 non-A from populations with a similar distribution of mutations. Hum Mutat 16:177, 2000.

Lipoprotein(A) levels and apoprotein(a) phenotypes in a Sicilian population.

The aim of this study was to evaluate the influence of lipoprotein(a) levels and apoprotein(a) isoform size in determining the low cardiovascular risk of a rural, inland Sicilian population. Plasma levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, lipoprotein(a) and apoprotein B and AI were measured in a sample of 278 subjects (141 males, 137 females) representative of a population of 1351 subjects (622 males, 729 females). The apoprotein(a) isoforms were also identified. Results indicated that the levels of the common lipo-apoliproprotein parameters were lower than those of other populations, while lipoprotein(a) plasmatic levels and apoprotein(a) isoform distribution were similar to those of other Caucasian populations. The distribution of lipoprotein(a) levels was skewed to the right, with a higher prevalence of low levels, the apoprotein(a) isoforms most strongly represented in our sample were of intermediate size (25-27 kringles IV). Univariate analysis showed that lipoprotein(a) levels were correlated to apoprotein(a) isoform size (R = -0.48, p < 0.001) and to the age of the subjects (R = +0.13, p < 0.01). In a multiple regression analysis, lipoprotein(a) levels were correlated to the apoprotein(a) isoform size of the homozygous isoforms or smaller heterozygous isoforms, while larger heterozygous forms were not correlated. In conclusion, our study showed that in our population, lipoprotein(a) levels and apoprotein(a) isoforms are similar to those of other Caucasian populations. Other factors, such as the physical activity of a rural population or the Mediterranean diet, must be considered in order to explain the lower cardiovascular risk of this population.

Autosomal dominant and sporadic radio-ulnar synostosis.

We report on seven cases of congenital radio-ulnar synostosis (RUS). Five were found in the same family and two were sporadic. In six the synostosis was bilateral and consistently involved the proximal end of the radius and ulna. In the familial cases the anomaly was inherited as an autosomal dominant trait and was associated with a Dubois sign and relative shortness of metacarpals number 4 and 5 in two patients, and of number 2 in another patient, and of all phalanges of the 5th fingers. These observations suggest involvement of an ulnar developmental field. RUS does not seem to be rare in the Sicilian population.