European journal of human genetics: EJHG

Publications in this journal

• Article: Reply to Townsend et al.

  Carmen Ayuso, José M Millán, Marta Mancheño, Rafael Dal-Ré
  European journal of human genetics: EJHG 05/2013;
• Article: Expanding the phenotype of IQSEC2 mutations: truncating mutations in severe intellectual disability.

  Frederic Tran Mau-Them, Marjolaine Willems, Beate Albrecht, Elodie Sanchez, Jacques Puechberty, Sabine Endele, Anouck Schneider, Nathalie Ruiz Pallares, Chantal Missirian, Francois Rivier, Manon Girard, Muriel Holder, Sylvie Manouvrier, Isabelle Touitou, Genevieve Lefort, Pierre Sarda, Anne Moncla, Severine Drunat, Dagmar Wieczorek, David Genevieve
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  ABSTRACT: Intellectual disability (ID) is frequent in the general population, with 1 in 50 individuals directly affected worldwide. The multiple etiologies include X-linked ID (XLID). Among syndromic XLID, few syndromes present severe ID associated with postnatal microcephaly and midline stereotypic hand movements. We report on three male patients with ID, midline stereotypic hand movements, hypotonia, hyperkinesia, strabismus, as well as seizures (2/3), and non-inherited and postnatal onset microcephaly (2/3). Using array CGH and exome sequencing we characterised two truncating mutations in IQSEC2, namely two de novo intragenic duplication mapped to the Xp11.22 region and a nonsense mutation in exon 7. We propose that truncating mutations in IQSEC2 are responsible for syndromic severe ID in male patients and should be screened in patients without mutations in MECP2, FOXG1, CDKL5 and MEF2C.European Journal of Human Genetics advance online publication, 15 May 2013; doi:10.1038/ejhg.2013.113.
  European journal of human genetics: EJHG 05/2013;
• Article: Autonomy and the patient's right 'not to know' in clinical whole-genomic sequencing.

  Anne Townsend, Francois Rousseau, Jan Friedman, Shelin Adam, Zoe Lohn, Patricia Birch
  European journal of human genetics: EJHG 05/2013;
• Article: A novel ALMS1 splice mutation in a non-obese juvenile-onset insulin-dependent syndromic diabetic patient.

  May Sanyoura, Cédric Woudstra, George Halaby, Patrick Baz, Valérie Senée, Pierre-Jean Guillausseau, Pierre Zalloua, Cécile Julier
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  ABSTRACT: Insulin-dependent juvenile-onset diabetes may occur in the context of rare syndromic presentations suggesting monogenic inheritance rather than common multifactorial autoimmune type 1 diabetes. Here, we report the case of a Lebanese patient diagnosed with juvenile-onset insulin-dependent diabetes presenting ketoacidosis, early-onset retinopathy with optic atrophy, hearing loss, diabetes insipidus, epilepsy, and normal weight and stature, who later developed insulin resistance. Despite similarities with Wolfram syndrome, we excluded the WFS1 gene as responsible for this disease. Using combined linkage and candidate gene study, we selected ALMS1, responsible for Alström syndrome, as a candidate gene. We identified a novel splice mutation in intron 18 located 3 bp before the intron-exon junction (IVS18-3T>G), resulting in exon 19 skipping and consequent frameshift generating a truncated protein (V3958fs3964X). The clinical presentation of the patient significantly differed from typical Alström syndrome by the absence of truncal obesity and short stature, and by the presence of ketoacidotic insulin-dependent diabetes, optic atrophy and diabetes insipidus. Our observation broadens the clinical spectrum of Alström syndrome and suggests that ALMS1 mutations may be considered in patients who initially present with an acute onset of insulin-dependent diabetes.European Journal of Human Genetics advance online publication, 8 May 2013; doi:10.1038/ejhg.2013.87.
  European journal of human genetics: EJHG 05/2013;
• Article: CHEK2*1100delC homozygosity in the Netherlands-prevalence and risk of breast and lung cancer.

  Petra Ea Huijts, Antoinette Hollestelle, Brunilda Balliu, Jeanine J Houwing-Duistermaat, Caro M Meijers, Jannet C Blom, Bahar Ozturk, Elly Mm Krol-Warmerdam, Juul Wijnen, Els Mjj Berns, John Wm Martens, Caroline Seynaeve, Lambertus A Kiemeney, Henricus F van der Heijden, Rob Aem Tollenaar, Peter Devilee, Christi J van Asperen
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  ABSTRACT: The 1100delC mutation in the CHEK2 gene has a carrier frequency of up to 1.5% in individuals from North-West Europe. Women heterozygous for 1100delC have an increased breast cancer risk (odds ratio 2.7). To explore the prevalence and clinical consequences of 1100delC homozygosity in the Netherlands, we genotyped a sporadic breast cancer hospital-based cohort, a group of non-BRCA1/2 breast cancer families, and breast tumors from a tumor tissue bank. Three 1100delC homozygous patients were found in the cohort of 1434 sporadic breast cancer patients, suggesting an increased breast cancer risk for 1100delC homozygotes (odds ratio 3.4, 95% confidence interval 0.4-32.6, P=0.3). Another 1100delC homozygote was found in 592 individuals from 108 non-BRCA1/2 breast cancer families, and two more were found after testing 1706 breast tumors and confirming homozygosity on their wild-type DNA. Follow-up data was available for five homozygous patients, and remarkably, three of them had developed contralateral breast cancer. A possible relationship between 1100delC and lung cancer risk was investigated in 457 unrelated lung cancer patients but could not be confirmed. Due to the small number of 1100delC homozygotes identified, the breast cancer risk estimate associated with this genotype had limited accuracy but is probably higher than the risk in heterozygous females. Screening for CHEK2 1100delC could be beneficial in countries with a relatively high allele frequency.European Journal of Human Genetics advance online publication, 8 May 2013; doi:10.1038/ejhg.2013.85.
  European journal of human genetics: EJHG 05/2013;
• Article: A framework to start the debate on neonatal screening policies in the EU: an Expert Opinion Document.

  Martina C Cornel, Tessel Rigter, Stephanie S Weinreich, Peter Burgard, Georg F Hoffmann, Martin Lindner, J Gerard Loeber, Kathrin Rupp, Domenica Taruscio, Luciano Vittozzi
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  ABSTRACT: The European Union (EU) Council Recommendation on rare diseases urged the member states to implement national and EU collaborative actions to improve the health care of rare disease patients. Following this recommendation, the European Commission launched a tender on newborn screening (NBS) to report on current practices of laboratory testing, form a network of experts and provide guidance on how to further implement NBS screening in a responsible way, the latter of which was provided in an Expert Opinion document. After consultation of experts from EU member states, (potential) candidate member states and European Free Trade Association countries, in a consensus meeting in June 2011, 70 expert opinions were finalized. They included the need to develop case definitions for all disorders screened for to facilitate assessment and international outcome studies. Decision whether a screening program should be performed can be based on screening criteria updated from the traditional Wilson and Jungner (1968) criteria, relating to disease, treatment, test and cost. The interest of the child should be central in the assessment of pros and cons. A European NBS body should assess evidence on (new) screening candidate disorders. For rare conditions, best level evidence should be used. The health system should ensure treatment to cases diagnosed by screening, controlled and revised by follow-up outcome studies. Screening methodology should aim to avoid unintended findings, such as mild forms and carrier status information, as much as possible. Activities to improve NBS in Europe, such as training and scientific evaluation, could benefit from collaboration at EU level and beyond.European Journal of Human Genetics advance online publication, 8 May 2013; doi:10.1038/ejhg.2013.90.
  European journal of human genetics: EJHG 05/2013;
• Article: Clinical utility gene card for: Johanson-Blizzard syndrome.

  Maja Sukalo, Julia Mayerle, Martin Zenker
  European journal of human genetics: EJHG 05/2013;
• Article: Human X-chromosome inactivation pattern distributions fit a model of genetically influenced choice better than models of completely random choice.

  Nisa K E Renault, Sonja M Pritchett, Robin E Howell, Wenda L Greer, Carmen Sapienza, Karen Helene Orstavik, David C Hamilton
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  ABSTRACT: In eutherian mammals, one X-chromosome in every XX somatic cell is transcriptionally silenced through the process of X-chromosome inactivation (XCI). Females are thus functional mosaics, where some cells express genes from the paternal X, and the others from the maternal X. The relative abundance of the two cell populations (X-inactivation pattern, XIP) can have significant medical implications for some females. In mice, the 'choice' of which X to inactivate, maternal or paternal, in each cell of the early embryo is genetically influenced. In humans, the timing of XCI choice and whether choice occurs completely randomly or under a genetic influence is debated. Here, we explore these questions by analysing the distribution of XIPs in large populations of normal females. Models were generated to predict XIP distributions resulting from completely random or genetically influenced choice. Each model describes the discrete primary distribution at the onset of XCI, and the continuous secondary distribution accounting for changes to the XIP as a result of development and ageing. Statistical methods are used to compare models with empirical data from Danish and Utah populations. A rigorous data treatment strategy maximises information content and allows for unbiased use of unphased XIP data. The Anderson-Darling goodness-of-fit statistics and likelihood ratio tests indicate that a model of genetically influenced XCI choice better fits the empirical data than models of completely random choice.European Journal of Human Genetics advance online publication, 8 May 2013; doi:10.1038/ejhg.2013.84.
  European journal of human genetics: EJHG 05/2013;
• Article: EJHG to follow variation nomenclature and stimulate data reporting.

  Gertjan B van Ommen
  European journal of human genetics: EJHG 05/2013; 21(5):479.
• Article: Platelet defects in congenital variant of Rett syndrome patients with FOXG1 mutations or reduced expression due to a position effect at 14q12.

  Christophe Goubau, Koen Devriendt, Nathalie Van der Aa, An Crepel, Dagmar Wieczorek, Tjitske Kleefstra, Marjolein H Willemsen, Anita Rauch, Andreas Tzschach, Thomy de Ravel, Peter Leemans, Chris Van Geet, Gunnar Buyse, Kathleen Freson
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  ABSTRACT: The Forkhead box G1 (FOXG1) gene encodes a transcriptional repressor essential for early development of the telencephalon. Intragenic mutations and gene deletions leading to haploinsufficiency cause the congenital variant of Rett syndrome. We here describe Rett syndrome-like patients, three of them carrying a balanced translocation with breakpoint in the chromosome 14q12 region, and one patient having a 14q12 microdeletion excluding the FOXG1 gene. The hypothesis of long-range FOXG1-regulatory elements in this region was supported by our finding of reduced FOXG1 mRNA and protein levels in platelets and skin fibroblasts from these cases. Given that FOXG1 is not only expressed in brain but also in platelets, we have studied platelet morphology in these patients and two additional patients with FOXG1 mutations. Electron microscopy of their platelets showed some enlarged, rounder platelets with often abnormal alpha, and fewer dense granules. Platelet function studies were possible in one 14q12 translocation patient with a prolonged Ivy bleeding time and a patient with a heterozygous FOXG1 c.1248C>G mutation (p.Tyr416X). Both have a prolonged PFA-100 occlusion time with collagen and epinephrine and reduced aggregation responses to low dose of ADP and epinephrine. Dense granule ATP secretion was normal for strong agonists but absent for epinephrine. In conclusion, our study shows that by using platelets functional evidence of cis-regulatory elements in the 14q12 region result in reduced FOXG1 levels in patients' platelets having translocations or deletions in that region. These platelet functional abnormalities deserve further investigation regarding a non-transcriptional regulatory role for FOXG1 in these anucleated cells.European Journal of Human Genetics advance online publication, 1 May 2013; doi:10.1038/ejhg.2013.86.
  European journal of human genetics: EJHG 05/2013;
• Article: Pre-symptomatic genetic testing for inherited cardiac conditions: a qualitative exploration of psychosocial and ethical implications.

  Elizabeth Ormondroyd, Stephanie Oates, Michael Parker, Edward Blair, Hugh Watkins
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  ABSTRACT: Inherited cardiac conditions (ICCs) can lead to sudden cardiac death at any age, yet are often asymptomatic and clinically undetected. Prophylactic interventions are available and cascade testing is recommended to identify family members at risk. When a disease-causing mutation has been identified in a family, pre-symptomatic genetic testing (PSGT) is available. This study explores perceptions of the cascade process, impact of PSGT and attitudes towards direct contact as an alternative to family-mediated dissemination for ICCs. In depth, interviews were conducted with 22 participants eligible for PSGT for Hypertrophic Cardiomyopathy or Long QT syndrome. Data were analysed using an inductive, thematic approach. Risk is perceived to be low pre-test in the absence of symptoms, and participants frequently test with the aim of ruling out risk to self and children. Testing of children is a complex decision; although older participants have concerns about possible adverse effects of genetic testing early in the life course, young participants are pragmatic about their result. The meaning of a positive genetic test result may be difficult to conceptualise in the absence of clinical evidence of disease, and this may deter further dissemination to at-risk family members. A majority of participants see advantages in direct contact from health professionals and support it in principle. Implications for practice include addressing risk perception pre-test, and presenting genetic test information as part of a risk stratification process rather than a binary outcome. Families may require more support or intervention in cascading genetic test information.European Journal of Human Genetics advance online publication, 1 May 2013; doi:10.1038/ejhg.2013.81.
  European journal of human genetics: EJHG 05/2013;
• Article: Reciprocal deletion and duplication at 2q23.1 indicates a role for MBD5 in autism spectrum disorder.

  Sureni V Mullegama, Jill A Rosenfeld, Carmen Orellana, Bregje W M van Bon, Sara Halbach, Elena A Repnikova, Lauren Brick, Chumei Li, Lucie Dupuis, Monica Rosello, [......], Kory Keller, Jonathan Zonana, Stuart Schwartz, Robert E Pyatt, Darrel J Waggoner, Lisa G Shaffer, Angela E Lin, Bert B A de Vries, Roberto Mendoza-Londono, Sarah H Elsea
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  ABSTRACT: Copy number variations associated with abnormal gene dosage have an important role in the genetic etiology of many neurodevelopmental disorders, including intellectual disability (ID) and autism. We hypothesize that the chromosome 2q23.1 region encompassing MBD5 is a dosage-dependent region, wherein deletion or duplication results in altered gene dosage. We previously established the 2q23.1 microdeletion syndrome and report herein 23 individuals with 2q23.1 duplications, thus establishing a complementary duplication syndrome. The observed phenotype includes ID, language impairments, infantile hypotonia and gross motor delay, behavioral problems, autistic features, dysmorphic facial features (pinnae anomalies, arched eyebrows, prominent nose, small chin, thin upper lip), and minor digital anomalies (fifth finger clinodactyly and large broad first toe). The microduplication size varies among all cases and ranges from 68 kb to 53.7 Mb, encompassing a region that includes MBD5, an important factor in methylation patterning and epigenetic regulation. We previously reported that haploinsufficiency of MBD5 is the primary causal factor in 2q23.1 microdeletion syndrome and that mutations in MBD5 are associated with autism. In this study, we demonstrate that MBD5 is the only gene in common among all duplication cases and that overexpression of MBD5 is likely responsible for the core clinical features present in 2q23.1 microduplication syndrome. Phenotypic analyses suggest that 2q23.1 duplication results in a slightly less severe phenotype than the reciprocal deletion. The features associated with a deletion, mutation or duplication of MBD5 and the gene expression changes observed support MBD5 as a dosage-sensitive gene critical for normal development.European Journal of Human Genetics advance online publication, 1 May 2013; doi:10.1038/ejhg.2013.67.
  European journal of human genetics: EJHG 05/2013;
• Article: The KCNJ8-S422L variant previously associated with J-wave syndromes is found at an increased frequency in Ashkenazi Jews.

  Krishna R Veeramah, Tatiana M Karafet, Daniel Wolf, Ricardo A Samson, Michael F Hammer
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  ABSTRACT: J-wave syndromes have been associated with increased risk of ventricular fibrillation and sudden cardiac death. Previous studies have identified the KCNJ8-S422L variant in heterozygous form in individuals with J-wave syndromes. Its absence in over 1500 controls, coupled with in vitro analysis, have led to the conclusion that S422L is pathogenic. We previously performed whole-genome sequencing in a family quartet of Ashkenazi Jewish decent with no history of J-wave syndrome. Re-examination of these data reveals that both parents are heterozygous for the S422L variant, while the 12-year old son carries two copies - thus representing the first reported case of a S422L homozygote. In order to examine whether the S422L mutation might segregate at appreciable frequencies in specific populations, we genotyped the variant in a panel consisting of 722 individuals from 22 European, Middle Eastern non-Jewish, Ashkenazi Jewish, and non-Ashkenazi Jewish populations. We found that the S422L allele was at a significantly higher frequency in Ashkenazi Jews (∼4%) compared with other populations in our survey, which have frequencies <0.25%. We also performed ECGs in both male members of the family quartet. The homozygous boy demonstrated no clinically significant ECG abnormalities, while the heterozygous father presented with a subtle J-wave point elevation. Our results suggest that either (a) previous studies implicating S422L as pathogenic for J-wave syndromes failed to appropriately account for European population structure and the variant is likely benign, or (b) Ashkenazi Jews may be at significantly increased risk of J-wave syndromes and ultimately sudden cardiac death.European Journal of Human Genetics advance online publication, 1 May 2013; doi:10.1038/ejhg.2013.78.
  European journal of human genetics: EJHG 05/2013;
• Article: Whole-exome sequencing, without prior linkage, identifies a mutation in LAMB3 as a cause of dominant hypoplastic amelogenesis imperfecta.

  James A Poulter, Walid El-Sayed, Roger C Shore, Jennifer Kirkham, Chris F Inglehearn, Alan J Mighell
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  ABSTRACT: The conventional approach to identifying the defective gene in a family with an inherited disease is to find the disease locus through family studies. However, the rapid development and decreasing cost of next generation sequencing facilitates a more direct approach. Here, we report the identification of a frameshift mutation in LAMB3 as a cause of dominant hypoplastic amelogenesis imperfecta (AI). Whole-exome sequencing of three affected family members and subsequent filtering of shared variants, without prior genetic linkage, sufficed to identify the pathogenic variant. Simultaneous analysis of multiple family members confirms segregation, enhancing the power to filter the genetic variation found and leading to rapid identification of the pathogenic variant. LAMB3 encodes a subunit of Laminin-5, one of a family of basement membrane proteins with essential functions in cell growth, movement and adhesion. Homozygous LAMB3 mutations cause junctional epidermolysis bullosa (JEB) and enamel defects are seen in JEB cases. However, to our knowledge, this is the first report of dominant AI due to a LAMB3 mutation in the absence of JEB.European Journal of Human Genetics advance online publication, 1 May 2013; doi:10.1038/ejhg.2013.76.
  European journal of human genetics: EJHG 05/2013;
• Article: From evolutionary bystander to master manipulator: the emerging roles for the mitochondrial genome as a modulator of nuclear gene expression.

  Martin P Horan, Neil J Gemmell, Jonci N Wolff
  European journal of human genetics: EJHG 04/2013;
• Article: Homozygosity analysis in amyotrophic lateral sclerosis.

  Kin Mok, Hannu Laaksovirta, Pentti J Tienari, Terhi Peuralinna, Liisa Myllykangas, Adriano Chiò, Bryan J Traynor, Michael A Nalls, Nicole Gurunlian, Aleksey Shatunov, Gabriella Restagno, Gabriele Mora, P Nigel Leigh, Chris E Shaw, Karen E Morrison, Pamela J Shaw, Ammar Al-Chalabi, John Hardy, Richard W Orrell
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  ABSTRACT: Amyotrophic lateral sclerosis (ALS) may appear to be familial or sporadic, with recognised dominant and recessive inheritance in a proportion of cases. Sporadic ALS may be caused by rare homozygous recessive mutations. We studied patients and controls from the UK and a multinational pooled analysis of GWAS data on homozygosity in ALS to determine any potential recessive variant leading to the disease. Six-hundred and twenty ALS and 5169 controls were studied in the UK cohort. A total of 7646 homozygosity segments with length >2 Mb were identified, and 3568 rare segments remained after filtering 'common' segments. The mean total of the autosomal genome with homozygosity segments was longer in ALS than in controls (unfiltered segments, P=0.05). Two-thousand and seventeen ALS and 6918 controls were studied in the pooled analysis. There were more regions of homozygosity segments per case (P=1 × 10(-5)), a greater proportion of cases harboured homozygosity (P=2 × 10(-5)), a longer average length of segment (P=1 × 10(-5)), a longer total genome coverage (P=1 × 10(-5)), and a higher rate of these segments overlapped with RefSeq gene regions (P=1 × 10(-5)), in ALS patients than controls. Positive associations were found in three regions. The most significant was in the chromosome 21 SOD1 region, and also chromosome 1 2.9-4.8 Mb, and chromosome 5 in the 65 Mb region. There are more than twenty potential genes in these regions. These findings point to further possible rare recessive genetic causes of ALS, which are not identified as common variants in GWAS.European Journal of Human Genetics advance online publication, 24 April 2013; doi:10.1038/ejhg.2013.59.
  European journal of human genetics: EJHG 04/2013;
• Article: Determination of population origin: a comparison of autosomal SNPs, Y-chromosomal and mtDNA haplogroups using a Malagasy population as example.

  Micaela Poetsch, Aline Wiegand, Melanie Harder, Rowena Blöhm, Noel Rakotomavo, Sandra Freitag-Wolf, Nicole von Wurmb-Schwark
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  ABSTRACT: Y-chromosomal and mitochondrial DNA (mtDNA) polymorphisms have been used for population studies for a long time. However, there is another possibility to define the origin of a population: autosomal single-nucleotide polymorphisms (SNPs) whose allele frequencies differ considerably in different populations. In an attempt to compare the usefulness of these approaches we studied a population from Madagascar using all the three mentioned approaches. Former investigations of Malagasy maternal (mtDNA) and paternal (Y chromosome) lineages have led to the assumption that the Malagasy are an admixed population with an African and Asian-Indonesian heritage. Our additional study demonstrated that more than two-third of the Malagasy investigated showed clearly a West African genotype regarding only the autosomal SNPs despite the fact that 64% had an Asian mtDNA and more than 70% demonstrated an Asian-Indonesian heritage in either mtDNA or Y-chromosomal haplogroup or both. Nonetheless, the admixture of the Malagasy could be confirmed. A clear African or Asian-Indonesian heritage according to all the three DNA approaches investigated was only found in 14% and 1% of male samples, respectively. Not even the European or Northern African influences, detected in 9% of males (Y-chromosomal analysis) and 11% of samples (autosomal SNPs) were consistent. No Malagasy in our samples showed a European or Northern African origin in both categories. So, the analysis of autosomal SNPs could confirm the admixed character of the Malagasy population, even if it pointed to a greater African influence as detectable by Y-chromosomal or mtDNA analysis.European Journal of Human Genetics advance online publication, 24 April 2013; doi:10.1038/ejhg.2013.51.
  European journal of human genetics: EJHG 04/2013;
• Article: Germline copy number variation of genes involved in chromatin remodelling in families suggestive of Li-Fraumeni syndrome with brain tumours.

  Juliette Aury-Landas, Gaëlle Bougeard, Hélène Castel, Hector Hernandez-Vargas, Aurélie Drouet, Jean-Baptiste Latouche, Marie-Thérèse Schouft, Claude Férec, Dominique Leroux, Christine Lasset, Isabelle Coupier, Olivier Caron, Zdenko Herceg, Thierry Frebourg, Jean-Michel Flaman
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  ABSTRACT: Germline alterations of the tumour suppressor TP53 gene are detected approximately in 25% of the families suggestive of Li-Fraumeni syndrome (LFS), characterised by a genetic predisposition to a wide tumour spectrum, including soft-tissue sarcomas, osteosarcomas, premenopausal breast cancers, brain tumours, adrenocortical tumours, plexus choroid tumours, leukaemia and lung cancer. The aim of this study was to determine the contribution of germline copy number variations (CNVs) to LFS in families without detectable TP53 mutation. Using a custom-designed high-resolution array CGH, we evaluated the presence of rare germline CNVs in 64 patients fulfilling the Chompret criteria for LFS, but without any detectable TP53 alteration. In 15 unrelated patients, we detected 20 new CNVs absent in 600 controls. Remarkably, in four patients who had developed each brain tumour, the detected CNV overlap the KDM1A, MTA3, TRRAP or SIRT3 genes encoding p53 partners involved in histone methylation or acetylation. Focused analysis of SIRT3 showed that the CNV encompassing SIRT3 leads to SIRT3 overexpression, and that in vitro SIRT3 overexpression prevents apoptosis, increases G2/M and results in a hypermethylation of numerous genes. This study supports the causal role of germline alterations of genes involved in chromatin remodelling in genetic predisposition to cancer and, in particular, to brain tumours.European Journal of Human Genetics advance online publication, 24 April 2013; doi:10.1038/ejhg.2013.68.
  European journal of human genetics: EJHG 04/2013;
• Article: Clinical utility gene card for: Alström syndrome - update 2013.

  Jan D Marshall, Pietro Maffei, Sebastian Beck, Timothy G Barrett, Richard Paisey, Jürgen K Naggert
  European journal of human genetics: EJHG 04/2013;