Cypriot Family Research Articles

‘How to Live Splendidly’: Strategies Towards Accumulation of Wealth in fifteenth-century Cyprus

ABSTRACT This article traces the strategies followed by two family groups towards wealth accumulation in fifteenth-century Cyprus, by examining their marriage alliances, wider kinship relations and shifting religious alignments. The fifteenth century was a testing time for the inhabitants of the island, as they experienced successive bouts of plague epidemics and foreign invasion (Mamluks 1424-26), as well as suffering the effects of civil war. While the fortunes of some Cypriot families declined, others successfully navigated the shifting power balances. Zooming out, they paper will re-assess the island's place within the business and trading networks, which stretched across the Mediterranean.

A Novel SPG7 Gene Pathogenic Variant in a Cypriot Family With Autosomal Recessive Spastic Ataxia.

The SPG7 gene encodes the paraplegin protein, an inner mitochondrial membrane—localized protease. It was initially linked to pure and complicated hereditary spastic paraplegia with cerebellar atrophy, and now represents a frequent cause of undiagnosed cerebellar ataxia and spastic ataxia. We hereby report the molecular characterization and the clinical features of a large Cypriot family with five affected individuals presenting with spastic ataxia in an autosomal recessive transmission mode, due to a novel SPG7 homozygous missense variant. Detailed clinical histories of the patients were obtained, followed by neurological and neurophysiological examinations. Whole exome sequencing (WES) of the proband, in silico gene panel analysis, variant filtering and family segregation analysis of the candidate variants with Sanger sequencing were performed. RNA and protein expression as well as in vitro protein localization studies and mitochondria morphology evaluation were carried out towards functional characterization of the identified variant. The patients presented with typical spastic ataxia features while some intrafamilial phenotypic variation was noted. WES analysis revealed a novel homozygous missense variant in the SPG7 gene (c.1763C > T, p. Thr588Met), characterized as pathogenic by more than 20 in silico prediction tools. Functional studies showed that the variant does not affect neither the RNA or protein expression, nor the protein localization. However, aberrant mitochondrial morphology has been observed thus indicating mitochondrial dysfunction and further demonstrating the pathogenicity of the identified variant. Our study is the first report of an SPG7 pathogenic variant in the Cypriot population and broadens the spectrum of SPG7 pathogenic variants.

A Novel CLN6 Variant Associated With Juvenile Neuronal Ceroid Lipofuscinosis in Patients With Absence of Visual Loss as a Presenting Feature.

The neuronal ceroid lipofuscinoses (NCLs), also known as Batten disease, are a group of autosomal recessive lysosomal storage disorders that are characterized by neurodegeneration, progressive cognitive decline, motor impairment, ataxia, loss of vision, seizures, and premature death. To date, pathogenic variants in more than 13 genes have been associated with NCLs. CLN6 encodes an endoplasmic reticulum non-glycosylated transmembrane protein, which is involved in lysosomal acidification. Mutations in CLN6 cause late-infantile juvenile NCL (JNCL) adult-onset NCL, and Kufs disease. Members from two available families with JNCL were clinically evaluated, and samples were collected from consenting individuals. The molecular investigation was performed by whole-exome sequencing, Sanger sequencing, and family segregation analysis. Furthermore, in silico prediction analysis and structural modeling of the identified CLN6 variants were performed. We report clinical and genetic findings of three patients from two Greek-Cypriot families (families 915 and 926) with JNCL. All patients were males, and the first symptoms appeared at the age of 6 years. The proband of family 926 presented with loss of motor abilities, ataxia, spasticity, seizure, and epilepsy. The proband of family 915 had ataxia, spasticity, dysarthria, dystonia, and intellectual disability. Both probands did not show initial signs of vision and/or hearing loss. Molecular analysis of family 926 revealed two CLN6 biallelic variants: the novel, de novo p.Tyr295Cys and the known p.Arg136His variants. In family 915, both patients were homozygous for the p.Arg136His CLN6 variant. Prediction analysis of the two CLN6 variants characterized them as probably damaging and disease-causing. Structural modeling of the variants predicted that they probably cause protein structural differentiation. In conclusion, we describe two unrelated Cypriot families with JNCL. Both families had variants in the CLN6 gene; however, they presented with slightly different symptoms, and notably none of the patients has loss of vision. In silico prediction and structural analyses indicate that both variants are most likely pathogenic.

Family across borders social capital and diaspora entrepreneurial preparedness

PurposeThe purpose of this paper is to study the way in which family ties influence the entrepreneurial preparedness of the diaspora family business owner.Design/methodology/approachIn-depth interviews were carried out with 15 Cypriot family business owners hosted in various countries. The paper draws on social capital theory and uses an abductive analytical approach.FindingsThe findings of this paper illustrate that family ties coming from the family across borders play a significant role for diaspora family business owners’ entrepreneurial preparedness. Hidden values deriving from the interpersonal relationships within the family across borders drive the diaspora family business owners to learn upon self-reflection and become entrepreneurially prepared, led by both urgency and esteem.Practical implicationsThis study provides practical implications for the entrepreneurial preparedness of diaspora family business owners and those who wish to become family business owners in a diaspora context.Originality/valueThis study contributes theoretically through the conceptualization of “family across borders social capital” and “diaspora entrepreneurial preparedness”. It also contributes empirically to the fields of diaspora family business, entrepreneurial learning and diaspora entrepreneurship through new knowledge regarding the role of family across borders social capital in the entrepreneurial preparedness of the diaspora family business owner.

The Story of a Ship Journey, Malaria, and the HBB Gene IVS-II-745 Mutation: Circassian Immigration to Cyprus.

Background During 19th century, the Circassians were secluded from their lands and forced to migrate to Ottoman Empire properties. Approximately 2,346 Circassians were exiled from Istanbul to Cyprus Island. During the deportation journey, many of Circassian passed away in consequence of malaria and unknown reasons. Overall, 1,351 survivor Circassians managed to reach the island, however, many of them had faced with endemic malaria again in Cyprus. An autosomal recessive hematological disorder thalassemia was the second endemic health condition after malaria, whereas thalassemia carriers show resistance to malaria infections. Materials and Methods A large Cypriot family with 57 members whose grandparents were supposed to be in that ship journey has been investigated in this study. Polymerase chain reaction (PCR)–amplification refractory mutation system (ARMS) analysis technique was used for genotyping the HHB gene. Results The human β-globin ( HBB ) gene c.316–106C > G (IVS-II-745) (II-745) heterozygous variation have been detected. Conclusion Overall, this study is a very good example for a typical natural selection. In this case, one single gene point mutation did not limit survival in the society; natively, it increased their survival changes to form new colonization and the inheritance of the mutation to the next generations.

THE IMPACT OF ASD ON MACEDONIAN FAMILIES AND THEIR EXPERIENCE OF PARENT EDUCATION

Autism spectrum disorder (ASD) is identified as having a significant impact on family life. Educating parents of children with ASD about the condition benefits both child and family. However, such programmes are typically unavailable in South-east Europe. To address this, the ESIPP project developed, provided and evaluated parent education for Croatian, Cypriot and Macedonian families, training 335 family members. A parent education curriculum and locally differentiated materials were developed, as well as recommendations for European policymakers. The project was evaluated using a mixed methods programme evaluation methodology in which families were surveyed regarding their experience of family life and the impact of parent education. This paper presents the findings of the study regarding the 70 Macedonian family members. Pre-training (n=70) and post training questionnaires (n=42) were completed, and semi-structured interviews were undertaken (n=16). The impact of ASD on quality of life, families’ experience of stigma and isolation, the inadequacy of professional support and the importance of family support are discussed. The positive impact of attending parent education is identified, as is its impact on parental happiness and relational issues and the need for continued parent and professional education regarding ASD.

Cypriot Emigration to the United States of America (1910-1930)

loannis Tserkezis, born in 1874, in Mazotos, a village in the Larnaca district of Cyprus, came from a poor family and was sent by his father to Smyrna, in 1888, aged 14, to seek employment to strengthen the family's income. The young Greek Cypriot's family was counting on help that would be provided to the young immigrant by his uncle (on his father 's side), who had been living in that multicultural Ottoman city for a considerable length of time. Despite his uncle 's efforts, the search for employment proved fruitless, and thus, after a brief period of time, Tserkezis was forced to return to his native country. He was not disheartened, though. He continued his efforts to find employment abroad during the years that followed. In 1899, he made efforts to settle in Alexandria and in 1902 went back to Smyrna, but both ventures proved unsuccessful. Up until then Tserkezis had chosen to emigrate to the most common destinations for the Cypriots of the time. That is, to Egypt or countries within the Ottoman Empire (Tserkezis 1988: 13-101).

Novel variants in the ACTA2 and MYH11 genes in a Cypriot family with thoracic aortic aneurysms: a case report

BackgroundThoracic aortic aneurysm (TAA) and/or thoracic aortic aneurysm and dissection (TAAD) is characterized by a considerable risk of morbidity and mortality of affected individuals. It is inherited in an autosomal dominant pattern and the 20% of patients with non-syndromic TAA have a positive family history. To date, the genetic basis of Cypriot patients with TAA has not been investigated. The purpose of this case report is to determine underlying genetic cause in this Cypriot family with TAA.Case presentationIn this report we present a patient with hyper-acute onset chest and back pain diagnosed with Type A Aortic Dissection with severe aortic valve regurgitation, who underwent emergency aortic surgery and Bentall procedure. Further investigation of the patient’s family was undertaken where both parents and an additional child were also found to be affected. A targeted sequencing panel including genes with known association to TAA was used to identify causative mutations in the index patient. Massively Parallel Sequencing results identified a frameshift deletion c.363_367del GAGTC, p.Met121Ilefs*5 in the ACTA2 gene and a non-synonymous variant c.3234C > G, p.Ile1078Met in the MYH11 gene. The presence or absence of these variants in the index patient and other family members was verified by Sanger sequencing. To our knowledge, this is the first report of a Cypriot family case diagnosed with TAA presented by two novel variants one in the ACTA2 and the other in the MYH11 genes.ConclusionsWe describe two novel variants in a Cypriot family with TAA that are potentially pathogenic, highlighting the importance of molecular genetic evaluation in families with TAA. These results may prove useful for screening purposes in Cypriot patients with non-syndromic familial TAA facilitating early identification of atrisk family members and direct intervention.

Molecular analysis of Cypriot families with aniridia reveals a novel PAX6 mutation.

The present study investigated the clinical and mutational spectrum of aniridia in a cohort of 17 affected individuals from six families from Cyprus. Each proband was initially evaluated for copy number variants at the PAX6 locus and subsequently underwent PAX6 mutation screening. Sequence analysis of FOXC1 and PITX2 was performed in patients who did not carry a PAX6 mutation. The most common clinical features in the group of aniridia patients associated with aniridia were nystagmus, cataracts and glaucoma. PAX6 pathogenic mutations were identified in five out of six families (a diagnostic yield of 84%). Previously reported pathogenic mutations in PAX6 were identified in four families, which comprise p.R203*, p.R240* and p.R317*. In addition, a novel pathogenic variant (p.E220Gfs*23) was identified in a single family. No pathogenic mutations were detected in PAX6, FOXC1 or PITX2 in the only patient with a sporadic form of aniridia-like phenotype, confirming the genetic heterogeneity associated with this disease. To the best of our knowledge this is the first report on the mutational spectrum of PAX6 in aniridia patients of Cypriot ancestry. Mutational screening of PAX6 serves a crucial role in distinguishing isolated from syndromic forms of aniridia, and it may therefore eliminate the need for renal ultrasound scan surveillance, delineate the phenotype and improve genetic counseling.

Multiple endocrine neoplasia 2 in Cyprus: evidence for a founder effect

PurposeMultiple endocrine neoplasia type 2 (MEN2) affects patients with RET proto-oncogene mutations. This cohort study refers to patients who were diagnosed with familial medullary thyroid carcinoma (MTC) and underwent RET genetic testing in Cyprus between years 2002 and 2017.Methods and patientsForty patients underwent RET testing by Sanger sequencing of exons 10–11 and 13–16. Genotyping with STR genetic markers flanking the RET gene along with Y-chromosome genotyping and haplogroup assignment was also performed.ResultsRET mutations were identified in 40 patients from 11 apparently unrelated Cypriot families and two non-familial sporadic cases. Nine probands (69.2%) were heterozygous for p.Cys618Arg, one (7.7%) for p.Cys634Phe, one (7.7%) for the somatic delE632-L633 and two (15.4%) for p.Met918Thr mutations. The mean age at MTC diagnosis of patients carrying p.Cys618Arg was 36.8 ± 14.2 years. The age of pheo diagnosis ranged from 26 to 43 years and appeared simultaneously with MTC in 5/36 (13.9%) cases. The high frequency of the p.Cys618Arg mutation suggested a possible ancestral mutational event. Haplotype analysis was performed in families with and without p.Cys618Arg. Six microsatellite markers covering the RET gene and neighboring regions identified one core haplotype associated with all patients carrying p.Cys618Arg mutation.ConclusionsThe mutation p.Cys618Arg is by far the most prevalent mutation in Cyprus followed by other reported mutations of variable clinical significance. The provided molecular evidence speculates p.Cys618Arg mutation as an ancestral mutation that has spread in Cyprus due to a possible founder effect.

Family support and early childhood education and care in Cyprus: existing policies and challenges

ABSTRACTAlthough wide family support policies are available to Cypriot families, Cyprus is among the countries with the least developed ECEC systems and the processes taken to address ECEC deficits is slow. Although female employment rates are slightly below the EU averages, there is a gap in the availability of childcare, an underinvestment in public ECEC and an inadequacy of policies in order to support mothers and families in general to balance their work and family lives. The present paper aims at shedding light on the complex and multi-layered aspects of reconciliation of paid work and care for children in Cyprus, presenting the family support measures available in Cyprus, as well as the provision of ECEC services. Existing policies and challenges are presented and discussed.

Knowledge and opinions of families regarding games—Toy selection for 6 to 12 year old children (the case of Northern Cyprus)

ABSTRACTGames and toys are irreplaceable basic needs of children of almost every age. They are also some of the most significant traces of culture. Some of our games and toys lost their original functions, and it is not remembered why they were functionally significant in Turkish Cypriot culture. Families and cultural identity also play a major role regarding different factors leading to changes in toy selection. The purpose of this study is to explore the knowledge and opinions of families regarding games and, in particular, toy selection for 6–12 year old children of Turkish Cypriot families. A survey was administered to 100 households in North Cyprus, and was used as a data collection tool. It was found that the most important factors in the selection of children’s games and toys were (1) the economic opportunities, and (2) children’s desires for toys after seeing them with their friends. A considerable number of families in Northern Cyprus see game-toy selection as important in a child’s social, psychomotor, mental, and cultural construction. Families, especially those living with difficulties, indicated that they cannot afford enough time to encourage playing traditional games. Although new versions of traditional games and toys are being developed and used, it is seen that educated and high-income families are more conscious about the importance of having information about them than others.

A novel COL4A1 frameshift mutation in familial kidney disease: the importance of the C-terminal NC1 domain of type IV collagen.

BackgroundHereditary microscopic haematuria often segregates with mutations of COL4A3, COL4A4 or COL4A5 but in half of families a gene is not identified. We investigated a Cypriot family with autosomal dominant microscopic haematuria with renal failure and kidney cysts.MethodsWe used genome-wide linkage analysis, whole exome sequencing and cosegregation analyses.ResultsWe identified a novel frameshift mutation, c.4611_4612insG:p.T1537fs, in exon 49 of COL4A1. This mutation predicts truncation of the protein with disruption of the C-terminal part of the NC1 domain. We confirmed its presence in 20 family members, 17 with confirmed haematuria, 5 of whom also had stage 4 or 5 chronic kidney disease. Eleven family members exhibited kidney cysts (55% of those with the mutation), but muscle cramps or cerebral aneurysms were not observed and serum creatine kinase was normal in all individuals tested.ConclusionsMissense mutations of COL4A1 that encode the CB3 [IV] segment of the triple helical domain (exons 24 and 25) are associated with HANAC syndrome (hereditary angiopathy, nephropathy, aneurysms and cramps). Missense mutations of COL4A1 that disrupt the NC1 domain are associated with antenatal cerebral haemorrhage and porencephaly, but not kidney disease. Our findings extend the spectrum of COL4A1 mutations linked with renal disease and demonstrate that the highly conserved C-terminal part of the NC1 domain of the α1 chain of type IV collagen is important in the integrity of glomerular basement membrane in humans.

Genetic screening of EXT1 and EXT2 in Cypriot families with hereditary multiple osteochondromas.

The purpose of this study was to perform genetic screening of the exostosin 1 (EXT1) and exostosin 2 (EXT2) genes in Cypriot patients with a clinical diagnosis of hereditary multiple osteochondromas (HMO). Initially, mutation analysis of the EXT1 gene was performed by Sanger sequencing. When no point mutation was identified in EXT1, EXT2 analysis was performed. When no sequence variant was identified in either of the candidate genes, array-comparative genomic hybridization (CGH) was implemented to detect any large copy number changes (CNCs). In total, three point mutations and a large deletion were identified in EXT1: the c.2101C>T(p.Arg701*) mutation and the ∼0.16-Mb deletion removing exons 2–11, which were previously reported whereas the c.486_489delCAGA(p.Asp162Glyfs*12) and the c.868G>T(p.Glu290*) mutations which were novel. It is the first report on genetic screening of five HMO patients of Cypriot descent. The observations presented provide additional evidence for the variability in phenotypic expression and the mutational spectrum of this disorder. The term HMO, or hereditary multiple exostoses (HME), MIM: 133700 and MIM: 133701 respectively is used to describe a genetic disorder characterized by the development of multiple, circumscript, occasionally painful and usually symmetric bony protuberances called osteochondromas (benign cartilaginous tumours which most frequently grow outward from the juxtaphyseal region of the long bones or

Cyprus and Its Places of Desire: Cultures of Displacement Among Greek and Turkish Refugees by Lisa Dikomitis (review)

Reviewed by: Cyprus and Its Places of Desire: Cultures of Displacement Among Greek and Turkish Refugees by Lisa Dikomitis Pafsanias Karathanasis (bio) Lisa Dikomitis, Cyprus and Its Places of Desire: Cultures of Displacement Among Greek and Turkish Refugees. London and New York: I. B. Tauris. 2012. Pp. ix + 229. 16 illustrations, 3 maps, 1 table. Cloth £59.50. In an ethnographic account of Cyprus at the edge of the sociopolitical transition manifested after the opening of the Cypriot border (the so called Green Line), Lisa Dikomitis works with Greek and Turkish Cypriot refugees who were forced to abandon their houses and villages during the turbulent decades of the 1960s and 1970s. It is a study of the material and symbolic importance that a single village located at the foot of the Pentadaktylos mountains holds for its former and current inhabitants. Before the Turkish military invasion of 1974 that displaced thousands of Greek Cypriots to the south, this village was named Larnakas tis Lapithou (Larnakas of Lapithos), and it was inhabited solely by Greek Cypriots. After 1974, however, the village was given the Turkish name Kozan and has been inhabited by Turkish Cypriot refugees, who left their villages in the Pafos district in southern Cyprus to resettle in the northern part of the divide under the protection of the Turkish army. Thus this account focuses on the collective experiences and the cultural memory of both refugee groups (namely the Larnatsjiotes and the Kozanlilar), who have strived to remake their lives and communities in their new homes, while at the same time keeping their former villages and houses in their minds and in their hearts. The author provides from the beginning a reflexive account on the ambivalent position of an anthropologist conducting fieldwork “at home” (24). Even if Cyprus is not where the researcher grew up, the island was present during her childhood as “home,” both through the summer visits to her Cypriot family and in the vivid descriptions of her Greek Cypriot father about Larnakas, his “village in paradise” (1–5). Thus the identity of the author as a “halfie” (22–23)—half Greek Cypriot, half Belgian—a term that she draws from Lila Abu-Lughod (1991), is well positioned and contextualized in the research field, providing a balanced account of the ways in which her identity acted both as a facilitator and as an obstacle during her fieldwork among relatives and non-relatives Cypriot refugees. As she explains, when someone conducts fieldwork among relatives and close friends and is warmly welcomed among them, she gains an immediate access to informants (24). However, following Neni Panourgiá (1995) and her fieldwork at (her) home in Athens, Dikomitis also recognizes that the stakes are high for the researcher because there is always a risk of “bruising the personal relationship” (24–25) with the loved ones. Dikomitis studies a central issue of the so-called Cyprus conflict in a period during which Cyprus went through an important sociopolitical transition. Both the 2003 easing of restrictions by the Turkish Cypriot regime on crossing the Cypriot border, which allowed people to visit the “other side” after nearly thirty years (the author uses the “other side” to mark both a geographical and a sociocultural line of crossing; 61), and the 2004 referendum on the United Nations Annan Plan for the solution of the Κυπριακό (Kypriako, Cyprus Problem) were developments that changed the sociopolitical landscape of Cyprus. The author’s account of the different Cypriot refugee understandings of their identity in relation to their “places of desire” (14–20) is provided in the aftermath of the 2003–2004 period. Thus the author had the privilege not only to study both refugee groups but also to accompany her informants during their first [End Page 397] emotional visits to their former villages. Moreover, she provides a structured outline of the changes in the attitudes of her informants after crossing the border became a reality and even an everyday routine for some groups of Greek and Turkish Cypriots. In this sense, it is a study of the “new Cyprus,” as Rebecca Bryant (2010) has called the country in the post-2004 era, which together with other works (Papadakis 2005, Constantinou 2007) points...

Combinatorial Conflicting Homozygosity (CCH) analysis enables the rapid identification of shared genomic regions in the presence of multiple phenocopies.

BackgroundThe ability to identify regions of the genome inherited with a dominant trait in one or more families has become increasingly valuable with the wide availability of high throughput sequencing technology. While a number of methods exist for mapping of homozygous variants segregating with recessive traits in consanguineous families, dominant conditions are conventionally analysed by linkage analysis, which requires computationally demanding haplotype reconstruction from marker genotypes and, even using advanced parallel approximation implementations, can take substantial time, particularly for large pedigrees. In addition, linkage analysis lacks sensitivity in the presence of phenocopies (individuals sharing the trait but not the genetic variant responsible). Combinatorial Conflicting Homozygosity (CCH) analysis uses high density biallelic single nucleotide polymorphism (SNP) marker genotypes to identify genetic loci within which consecutive markers are not homozygous for different alleles. This allows inference of identical by descent (IBD) inheritance of a haplotype among a set or subsets of related or unrelated individuals.ResultsA single genome-wide conflicting homozygosity analysis takes <3 seconds and parallelisation permits multiple combinations of subsets of individuals to be analysed quickly. Analysis of unrelated individuals demonstrated that in the absence of IBD inheritance, runs of no CH exceeding 4 cM are not observed. At this threshold, CCH is >97% sensitive and specific for IBD regions within a pedigree exceeding this length and was able to identify the locus responsible for a dominantly inherited kidney disease in a Turkish Cypriot family in which six out 17 affected individuals were phenocopies. It also revealed shared ancestry at the disease-linked locus among affected individuals from two different Cypriot populations.ConclusionsCCH does not require computationally demanding haplotype reconstruction and can detect regions of shared inheritance of a haplotype among subsets of related or unrelated individuals directly from SNP genotype data. In contrast to parametric linkage allowing for phenocopies, CCH directly provides the exact number and identity of individuals sharing each locus. CCH can also identify regions of shared ancestry among ostensibly unrelated individuals who share a trait. CCH is implemented in Python and is freely available (as source code) from http://sourceforge.net/projects/cchsnp/.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1360-4) contains supplementary material, which is available to authorized users.

The mutational spectrum of Lynch syndrome in cyprus.

Lynch syndrome is the most common form of hereditary colorectal cancer and is caused by germline mutations in the mismatch repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. Mutation carriers have an increased lifetime risk of developing colorectal cancer as well as other extracolonic tumours. The aim of the current study was to evaluate the frequency and distribution of mutations in the MLH1, MSH2 and MSH6 genes within a cohort of Cypriot families that fulfilled the revised Bethesda guidelines. The study cohort included 77 patients who fulfilled at least one of the revised Bethesda guidelines. Mutational analysis revealed the presence of 4 pathogenic mutations, 3 in the MLH1 gene and 1 in the MSH2 gene, in 5 unrelated individuals. It is noted that out of the 4 pathogenic mutations detected, one is novel (c.1610delG in exon 14 of the MLH1) and has been detected for the first time in the Cypriot population. Overall, the pathogenic mutation detection rate in our patient cohort was 7%. This percentage is relatively low but could be explained by the fact that the sole criterion for genetic screening was compliance to the revised Bethesda guidelines. Larger numbers of Lynch syndrome families and screening of the two additional predisposition genes, PMS2 and EPCAM, are needed in order to decipher the full spectrum of mutations associated with Lynch syndrome predisposition in Cyprus.

Novel homozygous PANK2 mutation causing atypical pantothenate kinase-associated neurodegeneration (PKAN) in a Cypriot family

Pantothenate kinase-associated neurodegeneration (PKAN) is the commonest, recessively inherited form of neurodegeneration with brain iron accumulation (NBIA) resulting from mutations in the pantothenate kinase 2 (PANK2) gene on chromosome 20. PKAN is usually rapidly progressive, presenting in the vast majority in the first decade of life (classic form). A rarer, later onset and slowly progressive (atypical) PKAN form also exists. We present two siblings of Cypriot descent, a 27-year-old man and his clinically asymptomatic younger sister, both of whom were found to be homozygous for a novel c.695A>G (p.Asp232Gly) missense mutation in exon 2 of the PANK2 gene. The index patient presented with a 5-year history of slowly progressive gait disturbance, dysarthria, mild axial rigidity and bradykinesia. His brain MRI scan revealed the characteristic “eye-of-the-tiger” sign. Atypical genetically confirmed PKAN cases are sparsely reported and should be considered in the differential diagnosis of patients presenting with a progressive extrapyramidal syndrome particularly if the radiographic findings are suggestive of iron accumulation. Effective treatment strategies for PKAN are not currently available and symptomatic therapy is often unsatisfactory. However, early diagnosis including the presymptomatic stage is important for genetic counseling and will be crucial for testing novel therapeutics in the future.

A NovelGBA2Gene Missense Mutation in Spastic Ataxia

Autosomal recessive cerebellar ataxias (ARCA) encompass a heterogeneous group of rare diseases that affect the cerebellum, the spinocerebellar tract and/or the sensory tracts of the spinal cord. We investigated a consanguineous Cypriot family with spastic ataxia, aiming towards identification of the causative mutation. Family members were clinically evaluated and studied at the genetic level. Linkage analysis at marker loci spanning known ARCA genes/loci revealed linkage to the APTX locus. Thorough investigation of the APTX gene excluded any possible mutation. Whole genome linkage screening using microsatellite markers and whole genome SNP homozygosity mapping using the Affymetrix Genome-Wide Human SNP Array 6.0 enabled mapping of the disease gene/mutation in this family to Chromosome 9p21.1-p13.2. Due to the large number of candidate genes within this region, whole-exome sequencing of the proband was performed and further analysis of the obtained data focused on the mapped interval. Further investigation of the candidate variants resulted in the identification of a novel missense mutation in the GBA2 gene. GBA2 mutations have recently been associated with hereditary spastic paraplegia and ARCA with spasticity. We hereby report a novel GBA2 mutation associated with spastic ataxia and suggest that GBA2 mutations may be a relatively frequent cause of ARCA.

The Burdensome and Depressive Experience of Caring

Family members of patients with chronic illnesses experience distress as a result of caregiving roles, which can be manifested as burden and depression, but cross-disease studies on how caring is experienced are limited. The present study was designed to examine the burden and psychiatric morbidity in the form of depression experienced by Cypriot families caring for a relative with one of the following: cancer, Alzheimer's disease, or schizophrenia. This study was cross-sectional, descriptive, and correlational. A total of 410 caregivers were recruited from the community. The research instruments included the Greek version of the Burden Interview and the Center of Epidemiological Studies-Depression Scale. Descriptive statistics, 1-way analysis of variance, and post hoc Tukey pairwise comparisons were used to examine significant differences between the 3 groups. The results indicate a high level of burden and depression among all caregivers. Significant differences (P < .001, F = 26.11) between the 3 caregiving groups were detected in terms of burden, with the highest reported for Alzheimer's disease caregivers. One-way analysis of variance showed significant differences (P = .008, F = 4.85) between the 3 caregiving groups in terms of depression, with the highest depression levels being for cancer caregivers. The findings increase our understanding about burden and emotional well-being in family caring for relatives with cancer and other chronic illnesses. The findings may be useful for health professionals to plan intervention strategies focusing on each domain of burden. The lessons learned from the caregiving role of family caregivers of patients with Alzheimer's disease or schizophrenia can be used to improve the caregiving process of patients with cancer.