Dutch Descent Research Articles

Identification of a novel locus for a USH3 like syndrome combined with congenital cataract

Usher syndrome (USH) is the most common genetic disease that causes both deafness and blindness. USH is divided into three types, USH1, USH2 and USH3, depending on the age of onset, the course of the disease, and on the degree of vestibular dysfunction. By homozygosity mapping of a consanguineous Danish family of Dutch descent, we have identified a novel locus for a rare USH3-like syndrome. The affected family members have a unique association of retinitis pigmentosa, progressive hearing impairment, vestibular dysfunction, and congenital cataract. The phenotype is similar, but not identical to that of USH3 patients, as congenital cataract has not been reported for USH3. By homozygosity mapping, we identified a 7.3 Mb locus on chromosome 15q22.2-23 with a maximum multipoint LOD score of 2.0. The locus partially overlaps with the USH1 locus, USH1H, a novel unnamed USH2 locus, and the non-syndromic deafness locus DFNB48.

Nevos melanocíticos numa comunidade de origem predominantemente holandesa no Brasil (1999-2007)

Epidemiological studies have shown a significant relationship between melanocytic nevi and cutaneous melanoma. To evaluate the development of melanocytic nevi in the pupils of a school composed primarily of children of Dutch descent and to assess the effect of environmental factors on these individuals whose phenotypic characteristics were similar to those of their ancestors. In 1999 a cohort study was initiated to count the number of melanocytic nevi in 282 pupils of 3 to 17 years of age, 53.9% of whom were boys. Five years later a repeat exam was conducted in 148 students of 8 to 22 years of age, 49.3% of whom were males. The association between the age, skin phototype, eye color, hair color and ethnic group of the pupils and their parents and the presence of melanocytic nevi was analyzed at the beginning and at the end of the study. There was a significant increase in cases of melanocytic nevi and dysplastic nevi at the follow-up examination. The number of melanocytic nevi was greater in boys than in girls in both covered and exposed areas of skin. Likelihood analysis calculated using the odds ratio showed that boys were more likely to develop melanocytic nevi than girls and that the children of non-mixed and mixed race with lighter hair were more likely to develop melanocytic nevi than those of other ethnic groups and those with dark hair. Children with skin phototype I were more likely to develop melanocytic nevi in covered areas of skin compared to those with skin types II or III. These data show that individuals of Dutch descent were more likely to develop melanocytic nevi than individuals of other ethnic origins.

'There is no love here anyway.' Sexuality, identity and HIV prevention in an African sub-culture in Amsterdam, The Netherlands

Undocumented African immigrants in The Netherlands are persons perceived to be at high-risk for HIV infection and yet are also a group that health care providers find difficult to access. The present study explores the experiences of a sample of undocumented African immigrants living in Amsterdam and offers recommendations aimed at providing more effective prevention interventions. Data collection occurred through interviews and focus groups with men and women aged 20-35 of both African and Dutch descent, using their interactions to explore possible communication challenges. Field notes of interviews were transcribed and analysed to identify emergent themes and patterns. A conceptual framework related to power and identity construction was adopted. The findings of the present study show how identity is shaped and constrained by discourses around sexuality and health, as well as what participants perceived to be conflicting belief systems, as well as the Dutch socioeconomic context. The data were divided into two broad categories: challenges around Dutch prevention interventions and challenges around peer-support. Each category is structured around sub-themes, such as 'concepts used in prevention messages', 'inter-cultural tension', 'identification with the educator' and 'stigma: roots and implications'. These findings indicate that issues of power and identity construction have great implications for the uptake of HIV prevention strategies by African immigrant groups and reveal important opportunities on which to focus prevention efforts.

Large ethnic variations in recommended physical activity according to activity domains in amsterdam, the netherlands

PurposeThe level of recommended physical activity (PA) is met less frequently by people from some ethnic minorities than others. We explored whether these differences in recommended PA between ethnic minority groups and the general population varied by domain and type of culturally-specific activity.MethodsParticipants were sampled from the population based SUNSET study and were from ethnic Dutch (n = 567), Hindustani-Surinamese (n = 370) and African-Surinamese (n = 689) descent. The validated SQUASH-questionnaire measured PA for the following domains: commuting, occupation, household, leisure time. Culturally-specific activities were added as extra question within the leisure time domain. The effect of each domain on ethnic differences in recommended PA prevalence was examined by odds-ratio (OR) analysis through recalculating recommended PA, while, in turn, excluding the contribution of each domain.ResultsIn the ethnic Dutch population, more vigorous PA in commuting and leisure time was reported compared to the Surinamese groups. The Hindustani-Surinamese and African-Surinamese reported more walking as commuting activity, while the Dutch group reported cycling more frequently. Ethnic differences in recommended PA became smaller in both Surinamese groups compared with the Dutch after removing commuting activity, for example, in Hindustani-Surinamese men (OR = 0.92, 95%CI: 0.62-1.37 vs. OR = 1.33, 0.89-2.00) and women (OR = 1.61, 1.12-2.32 vs. OR = 2.03, 1.41-2.92). Removing occupational activity resulted in larger ethnic differences in both groups compared with the Dutch. Smaller effects were found for yoga and dancing, leisure time and household activities.ConclusionThis study shows that differences in PA between ethnic minority groups and the general population vary according to the activity domain. The results indicate that including all relevant domains and activities is essential for assessment of ethnic differences in recommended PA.

“Church, Family, Hard Work, and Dutch Clean”

This article pictures the youth memories of older Dutch-Americans who grew up in the “Dutch enclave” of Holland, Michigan (USA). This area is heavily populated by Dutch immigrants sharing traditional Calvinist religious values, norms, and beliefs. Findings are based on oral interviews among a sample of older respondents from the area (mean age is 81 yrs.). The study combines a generational approach with an oral history methodology. Results indicate that respondents cherish their formative years, their Calvinist Dutch-American upbringing, and feel that their socialization in strict values, norms and beliefs had lasting effects on their personal life course and life style. Of the two basic ingredients of their cultural identity – Dutch descent and Reformed religion – faith is far more important than ethnicity. Studying narrative youth memories of members of the oldest generation of (Dutch) Americans is a fascinating topic for social scientists as this generation is about to be replaced and their stories will soon be forgotten.

Vitamin B12 status in patients of Turkish and Dutch descent with depression: a comparative cross-sectional study

BackgroundStudies have shown a clear relationship between depressive disorders and vitamin B12 deficiency. Gastroenteritis and Helicobacter pylori infections can cause vitamin B12 deficiency. Helicobacter pylori infections are not uncommon among people of Turkish descent in The Netherlands.AimTo examine the frequency of vitamin B12 deficiency in depressive patients of Turkish descent and compare it to the frequency of vitamin B12 deficiency in depressive patients of Dutch descent.MethodsThe present study is a comparative cross-sectional study of 47 patients of Turkish descent and 28 of Dutch descent. The depressive disorder diagnosis and differential diagnosis were made using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition text revision (SCID). The severity of the depressive symptoms was determined using the Beck Depression Inventory (BDI) and the 21-item Hamilton Depression Rating Scale (HAM-D-21). Serum baseline vitamin B6 and B12, folic acid and total serum homocysteine (tHcy) levels were measured.ResultsThe average ages of the patients of Turkish and Dutch descent were 40.57 and 44.75 years, respectively. There were no demonstrable differences between the serum vitamin B6, folic acid and tHcy levels in the two groups. The serum vitamin B12 levels were however clearly lower in the patients of Turkish descent than in those of Dutch descent. Vitamin B12 deficiency was however observed in 14 patients of Turkish descent and 1 of Dutch descent. This difference was significant. On the BDI, the patients of Turkish descent scored significantly higher than those of Dutch descent. Patients with vitamin B12 deficiency and those with hyperhomocysteinaemia had a significantly higher BDI score than patients with normal vitamin B12 and homocysteine levels. No relationship was observed with vitamin B12 and tHcy.ConclusionVitamin B12 deficiency occurs more frequently in depressive patients of Turkish than of Dutch descent. This is why it is advisable to test the vitamin B12 serum level in depressive patients of Turkish descent.

Identification of novel Angiogenin (ANG) gene missense variants in German patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease characterized by the selective death of motor neurons in the motor cortex, brain stem and spinal cord. Recently, missense variants in the angiogenin gene (ANG), an angiogenic factor expressed in ventral horn motor neurons that is up-regulated by hypoxia, have been found in ALS patients of Irish/Scottish, North American, Italian, French and Dutch descent. To investigate the role of ANG in the German population, we screened for mutations by sequencing the entire coding region of the ANG gene in a large sample of 581 German ALS cases and 616 sex- and age-matched healthy controls. We identified two heterozygous missense variants, F(−13)L and K54E, in two German sporadic ALS cases but not in controls. Both missense variants are novel and have not been previously found in ALS cases. Our results suggest that missense variants in the ANG gene play a role in ALS in the German population and provide further evidence to support the hypothesis that angiogenic factors up-regulated by hypoxia are involved in the pathophysiology of ALS.Electronic supplementary materialThe online version of this article (doi:10.1007/s00415-009-5124-4) contains supplementary material, which is available to authorized users.

First language attrition and reversion among older migrants

Emigration usually requires speakers to become bilingual, and eventually they may even become dominant in their second language. This can lead to a gradual loss of proficiency in the first language, a phenomenon referred to as first language attrition. As migrants become elderly, however, they sometimes report a “reversion” in language dominance, whereby the second language, which they have used in their daily lives for years or decades, recedes and the first language becomes stronger again. There are largely anecdotal cases of communication between such speakers and their children who were not brought up to speak their parents' first language becoming impossible. It is, however, very difficult to separate fact from fiction in such reports. This article will give an overview of changes in lexical access and fluency in the first language of adult migrants. It will assess simplistic predictions for a linear development of first and second languages against a more complex perspective which takes into account psycholinguistic aspects of activation, inhibition, and cognitive ageing. The predictions made on this basis will be tested on a large-scale quantitative investigation of language proficiency among migrants of German and Dutch descent in the Netherlands and Canada.

Lamarckism Or Fear Of The Other And His Exclusion

The Republic of South Africa is the largest and most powerful of the nations situated in the southernmost part of Africa . It came into existence in 1910 through the union of the two British colonies of Cape of good Hope and Natal and the two former Africaner (Boer) republics of Orange free state and south African Republic of Transversal . In may 31 1961 these former loose states became the republic of South Africa . The Republic is made of racially and ethnically diversified population, Blacks, including those in black ethnic homelands make up 72.2% of the population. Coloured that is those of mixed racial origin is 9.1%, the Asians make up 2.8% while the white population is 15.9%, this is divided on linguistic and political lines between the Afrikaners mainly persons of Dutch descent and the English speakers mainly descendants of British settlers. The black population consists of nine main ethnic groups, the largest of which are the Zulu and Xhosa..IFE Psychologia – Special Issue: Xenophobia Vol. 16 (2) 2008: pp. 190-198

Recurrent CNVs Disrupt Three Candidate Genes in Schizophrenia Patients

Schizophrenia is a severe psychiatric disease with complex etiology, affecting approximately 1% of the general population. Most genetics studies so far have focused on disease association with common genetic variation, such as single-nucleotide polymorphisms (SNPs), but it has recently become apparent that large-scale genomic copy-number variants (CNVs) are involved in disease development as well. To assess the role of rare CNVs in schizophrenia, we screened 54 patients with deficit schizophrenia using Affymetrix's GeneChip 250K SNP arrays. We identified 90 CNVs in total, 77 of which have been reported previously in unaffected control cohorts. Among the genes disrupted by the remaining rare CNVs are MYT1L, CTNND2, NRXN1, and ASTN2, genes that play an important role in neuronal functioning but--except for NRXN1--have not been associated with schizophrenia before. We studied the occurrence of CNVs at these four loci in an additional cohort of 752 patients and 706 normal controls from The Netherlands. We identified eight additional CNVs, of which the four that affect coding sequences were found only in the patient cohort. Our study supports a role for rare CNVs in schizophrenia susceptibility and identifies at least three candidate genes for this complex disorder.

LG839: Anti-obesity effects and polymorphic gene correlates of reward deficiency syndrome

This study systematically assessed the weight management effects of a novel experimental DNA-customized nutraceutical, LG839 (LifeGen, Inc., La Jolla, CA, USA). A total of 1058 subjects who participated in the overall D.I.E.T. study were genotyped and administered an LG839 variant based on polymorphic outcomes. A subset of 27 self-identified obese subjects of Dutch descent, having the same DNA pattern of four out of the five candidate genes tested (chi-square analysis) as the entire data set, was subsequently evaluated. Simple t tests comparing a number of weight management parameters before and after 80 days of treatment with LG839 were performed. Significant results were observed for weight loss, sugar craving reduction, appetite suppression, snack reduction, reduction of late night eating (all P<0.01), increased perception of overeating, enhanced quality of sleep, increased happiness (all P<0.05), and increased energy (P<0.001). Polymorphic correlates were obtained for a number of genes (LEP, PPAR-gamma2, MTHFR, 5-HT2A, and DRD2 genes) with positive clinical parameters tested in this study. Of all the outcomes and gene polymorphisms, only the DRD2 gene polymorphism (A1 allele) had a significant Pearson correlation with days on treatment (r=0.42, P=0.045). If these results are confirmed in additional rigorous, controlled studies, we carefully suggest that DNA-directed targeting of certain regulator genes, along with customized nutraceutical intervention, provides a unique framework and strategic modality to combat obesity.

The Komedie Stamboel: Popular Theater in Colonial Indonesia, 1891-1903 (review)

Reviewed by: The Komedie Stamboel: Popular Theater in Colonial Indonesia, 1891-1903 Cobina Gillitt The Komedie Stamboel: Popular Theater in Colonial Indonesia, 1891-1903. By Matthew Isaac Cohen. Athens, OH: Ohio University Press. 2006. 473 pp. 36 black and white illus. 4 black and white maps. Appendix of Plays and Tableaux, Notes, Glossary, Selected Bibliography, and Index. Paper $30.00. The Komedie Stamboel: Popular Theater in Colonial Indonesia, 1891–1903 by Matthew Isaac Cohen may cover only a few years in Indonesia's theatre history, but those dozen years represent a crucial period that helped lay the foundation for a modern Indonesian nation that continues to be reflected today in contemporary Indonesian theatre and film. Cohen details his subject exhaustively and lovingly, giving the reader a vibrant, rich, and absorbing portrait of the founding, development, and influence of the Komedie Stamboel, a Malay-language musical theatre troupe founded in 1891 in the booming colonial harbor city of Surabaya on Java's east coast. Cohen, currently a senior lecturer in the Department of Drama and Theatre, Royal Holloway, University of London, has spent decades researching Indonesian performance and is an accomplished Cirebonese wayang kulit dalang (West Javanese rod puppeteer). Using his multilingual skills, he has explored and included every possible research avenue, and, as a result, is able to include previously untranslated primary materials from Dutch, Javanese, and Indonesian contemporaneous sources. With this book, Cohen has produced nothing less than the definitive work on the Komedie Stamboel, a neglected and more often than not glossed over yet key moment in Indonesian cultural history. The book is written in accessible prose and entertaining to boot. [End Page 155] After an introduction to the development of nineteenth-century popular theatre in the Netherlands Indies, the founding and development of the Komedie Stamboel is treated chronologically in five successive chapters beginning with an in-depth description of Surabaya in 1891, including its geography, ethnic populations, architecture, and cultural life, setting the stage for the troupe's heterogeneous beginnings. From its first performances of stories from The One Thousand and One Nights, Cohen describes in meticulous detail Komedie Stamboel's members, musicians, and audiences. At the same time, he elaborates on their social histories. The Komedie Stamboel is actually about more than the history of a theatrical company and its various incarnations under the leadership of actor-manager Auguste Mahieu (1865–1903), who is of Dutch and Javanese descent. It is an exploration of the Netherlands Indies' shift into a modern Indonesian nation state through a portrait of the different cultural constituencies that made up Surabaya and the world of popular performances at the turn of the twentieth century, especially the Indo—the Eurasians of (primarily) Dutch and Indonesian ancestry who were the main players and producers of Stamboel, and the Chinese who were the main financial backers. Cohen connects every aspect of Stamboel's productions to a wider cultural context. For example, when discussing the introduction of tableaux vivants into the addenda following a Komedie Stamboel performance, he traces the history of tableaux in European and American theatre, as well as a growing use of "pictorial illusionism" in other parts of Indonesia during the late nineteenth century (75). Every production mounted by the group is described in fascinating detail, down to the synopses of the plays, weather conditions at particular performances, the state of the road in front of the theatre building, the make-up of a particular night's audience, who was paid how much, petty squabbles between the actors, professional feuds between rival troupes, murders, and much more. All the personalities involved are presented three-dimensionally, as if Cohen personally knew each of them and was, in fact, there and is recounting this history from his experience of having attended the rehearsals, read each review hot off the press, toured with them throughout Java to Batavia, Solo, Semarang, Bogor, and Malang, among other cities, and overseas to Singapore as well. Chapter 6, "Mahieu's Legacy," Cohen extends his study to include the influence of stambul (as it became known) on twentieth century Indonesian theatre and film, as well as on state and identity politics. Komedie Stamboel has been both held up as...

A novel (Leu183Pro-)mutation in the HFE-gene co-inherited with the Cys282Tyr mutation in two unrelated Dutch hemochromatosis patients

We describe a novel heterozygous mutation in exon 3 of the HFE-gene that was co-inherited with Cys282Tyr in two unrelated Dutch men both presenting a classical form of hereditary hemochromatosis. Heterozygosity for this mutation was also found in one out of 100 healthy controls of Dutch descent. This c.548T>C mutation converts a leucine to a proline residue at position 183 in the α2-helix of the HFE-protein (Leu183Pro). Standard bioinformatics analysis shows that the mutation is likely to disturb the HFE interaction with TfR1. This disrupting role of the mutation in the iron regulatory pathway is further corroborated by the familial co-occurrence of the observed compound heterozygosity with increased serum iron parameters. Haplotype analysis strongly suggests that this novel mutation arose from a common ancestor in the distant past. These findings may have implications for HFE-testing of iron overloaded heterozygous Cys282Tyr-patients of Northern European origin and their relatives.

Narrative Accounts of Origins

This article uses a study of the life-story narratives of former classmates of Dutch and Moluccan descent to argue that the constructionist approach to intersectionality, with its account of identity as a narrative construction rather than a practice of naming, offers better tools for answering questions concerning intersectional identity formation than a more systemic intersectional approach. The case study also highlights the importance of the quest for origins in narratives. It demonstrates that theories of intersectionality are not justified in subsuming the issue of belonging under the identity marker of ethnicity, when all identities are performatively produced in and through narrative enactments that include the precarious achievement of belonging. The case study demonstrates that if narrative accounts of a (singular or collective) life fail to achieve narrative closure regarding roots, attempts to trace routes are seriously hampered.

South-Asian Type 2 Diabetic Patients Have Higher Incidence and Faster Progression of Renal Disease Compared With Dutch-European Diabetic Patients

Surinamese South-Asian migrants, living in the Netherlands and aged >30 years, have a nearly 40-fold increased age-adjusted risk for end-stage diabetic nephropathy in comparison with their European Dutch counterparts (1). Several studies in the U.K. also showed a higher incidence of end-stage renal failure in South-Asian diabetic patients (2,3,4,5,6). There is no clear explanation for the increased risk in South-Asian migrants, who originally descend from the Indian subcontinent. An earlier study showed no familial predisposition for renal disease in South-Asian migrants (7). There is a discrepancy between the reported eight-times higher prevalence of diabetes (8) and the 40-fold higher risk of end-stage diabetic nephropathy (1) in this population. This discrepancy could be explained by either a higher incidence of nephropathy in the Asian diabetic patients and/or faster progression to end-stage renal failure. We performed a cohort study in South-Asian and Dutch-European type 2 diabetic patients to compare differences in the incidence of microalbuminuria and progression of renal failure between both ethnic groups. We used the registry of the outpatient diabetic clinic of the Haga Teaching Hospital during the period of 1994–1996. Ethnicity was by self-report. Migrants who originally descend from the Indian subcontinent were reported as South-Asian. Patients who were of Dutch descent were reported as European. We selected a cohort of 149 South Asian type 2 diabetic patients and matched them for sex and level of urinary albumin excretion …

The frequent BRCA1 mutation 1135insA has multiple origins: a haplotype study in different populations

BackgroundAnalysis of the chromosomal background upon which a mutation occurs can be used to reconstruct the origins of specific disease-causing mutations. The relatively common BRCA1 mutation, 1135insA, has been previously identified as a Norwegian founder mutation. We performed haplotype analysis of individuals from breast and ovarian cancer families from four different ethnic backgrounds who had been identified as carriers of the BRCA1: 1135insA mutation.MethodsFour microsatellite markers (D17S855, D17S1322, D17S1323 and D17S1325) located within or near the BRCA1 gene were genotyped in mutation carriers from 6 families of French Canadian, Italian and Dutch descent. Haplotypes were inferred from the genotype data and compared between these families and with the previously reported Norwegian founder haplotype.ResultsThe 1135insA mutation was found to occur on three distinct haplotype backgrounds. The families from Norway shared a distinct haplotype while the families of French Canadian, Italian, and Dutch descent were found to occur on one of two additional, distinct backgrounds.ConclusionOur results indicate that while the Norwegian haplotype including 1135insA represents an ancient Norwegian mutation, the same mutation has occurred independently in the other populations examined. In centres where targeted mutation testing is performed, exclusively or prior to gene sequencing, our findings suggest that this recurring mutation should be included in targeted mutation panels, irrespective of the ethnic origin of the persons tested.

Travel and Translation in the Dance Writings of Beryl de Zoete

Around the time Marcia Siegel's dance writing career began, an important predecessor's ended with the death in 1962 of Beryl de Zoete, critic and ethnologist. Of Dutch descent, de Zoete was born in London in 1879 into a family of brokers whose name still figures prominently on the British stock exchange. Traveling independently, using her gifts for meeting people and learning languages, she wrote three unprecedented ethnographies, beginning with the book she produced with Walter Spies, Dance and Drama in Bali (1938), and followed by The Other Mind: A Study of Dance in South India (1953) and Dance and Magic Drama in Ceylon (1957). From the late 1920s through the mid-1950s, de Zoete also published many articles on her encounters with European dance and music, and her reviews of performances and books appeared regularly in newspapers, most notably in the influential weekly New Statesman and Nation. After she died, her friend Arthur Waley completed her planned collection of short pieces, The Thunder and the Freshness (1963), titled after poet John Keats's description of a waterfall. This image evoked, for her, the sound of dance drumming before dawn.In this talk, I sketch de Zoete's life and begin to think about how she worked as a writer. As part of my doctoral research, I investigated her connections with Dalcroze Eurhythmies, which teaches music through movement and improvisation. I also draw on previous work by Margaret Dale, who remembers de Zoete's visits to Sadler's Wells Ballet rehearsals in the 1940s and later consulted her about presenting Sinhalese dance on BBC television.

Identification of novel mutations in classical galactosemia

Classical galactosemia is an autosomal recessive disorder of galactose metabolism due to galactose-1-phosphate uridyltransferase (GALT) deficiency. Treatment through restriction of dietary galactose intake is lifesaving, but, in spite of this diet, most patients develop abnormalities. In this paper we report the mutational spectrum of classical galactosemia in a cohort of 123 Dutch patients, all with biochemically proven classical galactosemia. In the human GALT gene, which is located on chromosome 9p13, we identified 24 different mutations, including nine mutations that have not been reported previously. The novel mutations include five missense mutations (c.152G>A/p.R51Q, c.404C>T/p.S135W, c.687G>T/p.K229N, c.756G>T/p.Q252H, and c.1140A>C/p.X380C), a frame shift mutation (c.410dupT), a splice site mutation (c.821-2A>G), a possible branch point mutation (c.508-29delT), and a large deletion encompassing at least exons 1-11. Six of these novel mutations were found in patients of Dutch descent: p.R51Q, p.S135W, p.K229N, p.Q252H, p.X380C, and c.410dupT.

Abnormal hepatocystin caused by truncating PRKCSH mutations leads to autosomal dominant polycystic liver disease.

Mutations in protein kinase C substrate 80K-H (PRKCSH), encoding for the protein hepatocystin, cause autosomal dominant polycystic liver disease (PCLD), which is clinically characterized by the presence of multiple liver cysts. PCLD has been documented in families from Europe (Netherlands, Belgium, Finland) as well as from the United States. In this article, we report results from extensive mutational analysis of the PRKCSH gene in a group of 14 PCLD families and 65 singleton cases of Dutch and Finnish descent with multiple simple liver cysts. We identified PRKCSH mutations in 12 families and in 3 sporadic cases. In 8 of 10 Finnish families we detected the 1437+2delTG splice-site mutation. In Dutch families, we found 2 other mutations that affect correct splicing of PRKCSH: 292+1 G>C (2 families) and 1338-2 A>G (1 family). In another Dutch family, we detected a novel deletion (374-375delAG) in exon 6, predicting an abnormal shortened protein. Investigation of the carrier haplotypes identified a common founder chromosome in unrelated individuals in each of the 3 identified splice-site mutations. In 2 Finnish families with dominantly inherited PCLD, and in 62 of 65 sporadic cases with multiple simple liver cysts, we failed to demonstrate any PRKCSH mutation. This corroborates the notion that autosomal dominant PCLD is genetically heterogeneous. In conclusion, we propose that, on the basis of our results, genetic screening for PRKCSH gene mutations should be limited to patients either with a positive family history for PCLD or who have severe polycystic liver disease.

Evidence for linkage between juvenile myoclonic epilepsy-related idiopathic generalized epilepsy and 6p11-12 in Dutch families.

Previous linkage studies provided evidence for juvenile myoclonic epilepsy (JME) susceptibility loci at 6p11-12, HLA-6p21.3 region, 15q14, and 5q34. These results indicate locus heterogeneity or interpopulation differences, thus underlining the importance of replication studies. We describe a replication linkage study of the 6p-q13 region in 18 families ascertained from JME probands of Dutch descent. In the presence of heterogeneity, the definition of the disease status may be crucial, and we therefore used two disease phenotypes: narrow [JME/idiopathic generalized epilepsy (IGE)-"only"] and broad (JME/IGE-plus-fast EEG background activity). We found evidence of linkage at 6p11-12 in multipoint analyses (p < 0.01 in a replication study) for both these disease definitions. Analysis of this region, assuming heterogeneity and autosomal dominant inheritance with a conservative 60% of penetrance, gave a maximum multipoint parametric lod score of 2.07 at D6S1573 for the narrow phenotype and peaked at 2.53 between D6S1623 and D6S1573 for the broad phenotype. The p value for nonparametric linkage reached 0.0013 for the narrow phenotype and 0.0010 for the broad. Significant exclusion (lod score <or=2) was found for the HLA region and for 10 to 30 cM telomeric to HLA. Our results provide evidence for a susceptibility locus for JME/IGE-plus-fast EEG background activity at 6p11-12. Additionally, by using a narrow definition, we were able to confirm previous evidence for a JME-IGE locus at this location.