caa a22 4500 445861908 CHVBK 20180317145446.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s00439-010-0907-3 doi (NATIONALLICENCE)springer-10.1007/s00439-010-0907-3 Autosomal recessive mental retardation: homozygosity mapping identifies 27 single linkage intervals, at least 14 novel loci and several mutation hotspots [Elektronische Daten] [Andreas Kuss, Masoud Garshasbi, Kimia Kahrizi, Andreas Tzschach, Farkhondeh Behjati, Hossein Darvish, Lia Abbasi-Moheb, Lucia Puettmann, Agnes Zecha, Robert Weißmann, Hao Hu, Marzieh Mohseni, Seyedeh Abedini, Anna Rajab, Christoph Hertzberg, Dagmar Wieczorek, Reinhard Ullmann, Saghar Ghasemi-Firouzabadi, Susan Banihashemi, Sanaz Arzhangi, Valeh Hadavi, Gholamreza Bahrami-Monajemi, Mahboubeh Kasiri, Masoumeh Falah, Pooneh Nikuei, Atefeh Dehghan, Masoumeh Sobhani, Payman Jamali, Hans Ropers, Hossein Najmabadi] Mental retardation (MR) has a worldwide prevalence of around 2% and is a frequent cause of severe disability. Significant excess of MR in the progeny of consanguineous matings as well as functional considerations suggest that autosomal recessive forms of MR (ARMR) must be relatively common. To shed more light on the causes of autosomal recessive MR (ARMR), we have set out in 2003 to perform systematic clinical studies and autozygosity mapping in large consanguineous Iranian families with non-syndromic ARMR (NS-ARMR). As previously reported (Najmabadi et al. in Hum Genet 121:43-48, 2007), this led us to the identification of 12 novel ARMR loci, 8 of which had a significant LOD score (OMIM: MRT5-12). In the meantime, we and others have found causative gene defects in two of these intervals. Moreover, as reported here, tripling the size of our cohort has enabled us to identify 27 additional unrelated families with NS-ARMR and single-linkage intervals; 14 of these define novel loci for non-syndromic ARMR. Altogether, 13 out of 39 single linkage intervals observed in our cohort were found to cluster at 6 different loci on chromosomes, i.e., 1p34, 4q27, 5p15, 9q34, 11p11-q13 and 19q13, respectively. Five of these clusters consist of two significantly overlapping linkage intervals, and on chr 1p34, three single linkage intervals coincide, including the previously described MRT12 locus. The probability for this distribution to be due to chance is only 1.14×10−5, as shown by Monte Carlo simulation. Thus, in contrast to our previous conclusions, these novel data indicate that common molecular causes of NS-ARMR do exist, and in the Iranian population, the most frequent ones may well account for several percent of the patients. These findings will be instrumental in the identification of the underlying genes. Springer-Verlag, 2010 Kuss Andreas Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut Garshasbi Masoud Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut Kahrizi Kimia Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut Tzschach Andreas Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut Behjati Farkhondeh Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut Darvish Hossein Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut Abbasi-Moheb Lia Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut Puettmann Lucia Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut Zecha Agnes Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut Weißmann Robert Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut Hu Hao Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut Mohseni Marzieh Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut Abedini Seyedeh Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut Rajab Anna Genetics Unit, Ministry of Health, Directorate General of Health Affairs, Royal Hospital, Muscat, Sultanate of Oman aut Hertzberg Christoph Vivantes Klinikum Neukölln, Berlin, Germany aut Wieczorek Dagmar Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany aut Ullmann Reinhard Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut Ghasemi-Firouzabadi Saghar Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut Banihashemi Susan Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut Arzhangi Sanaz Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut Hadavi Valeh Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran aut Bahrami-Monajemi Gholamreza Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut Kasiri Mahboubeh Welfare Organization, Share Kord, Iran aut Falah Masoumeh Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut Nikuei Pooneh Welfare Organization, Bandar Abbas, Iran aut Dehghan Atefeh Welfare Organization, Yazd, Iran aut Sobhani Masoumeh Welfare Organization, Talesh, Iran aut Jamali Payman Welfare Organization, Shahroud, Iran aut Ropers Hans Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut Najmabadi Hossein Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut Human Genetics Springer-Verlag 129/2(2011-02-01), 141-148 0340-6717 129:2<141 2011 129 439 https://doi.org/10.1007/s00439-010-0907-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-010-0907-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kuss Andreas Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut NATIONALLICENCE 700 1- Garshasbi Masoud Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut NATIONALLICENCE 700 1- Kahrizi Kimia Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut NATIONALLICENCE 700 1- Tzschach Andreas Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut NATIONALLICENCE 700 1- Behjati Farkhondeh Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut NATIONALLICENCE 700 1- Darvish Hossein Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut NATIONALLICENCE 700 1- Abbasi-Moheb Lia Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut NATIONALLICENCE 700 1- Puettmann Lucia Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut NATIONALLICENCE 700 1- Zecha Agnes Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut NATIONALLICENCE 700 1- Weißmann Robert Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut NATIONALLICENCE 700 1- Hu Hao Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut NATIONALLICENCE 700 1- Mohseni Marzieh Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut NATIONALLICENCE 700 1- Abedini Seyedeh Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut NATIONALLICENCE 700 1- Rajab Anna Genetics Unit, Ministry of Health, Directorate General of Health Affairs, Royal Hospital, Muscat, Sultanate of Oman aut NATIONALLICENCE 700 1- Hertzberg Christoph Vivantes Klinikum Neukölln, Berlin, Germany aut NATIONALLICENCE 700 1- Wieczorek Dagmar Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany aut NATIONALLICENCE 700 1- Ullmann Reinhard Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut NATIONALLICENCE 700 1- Ghasemi-Firouzabadi Saghar Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut NATIONALLICENCE 700 1- Banihashemi Susan Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut NATIONALLICENCE 700 1- Arzhangi Sanaz Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut NATIONALLICENCE 700 1- Hadavi Valeh Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran aut NATIONALLICENCE 700 1- Bahrami-Monajemi Gholamreza Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut NATIONALLICENCE 700 1- Kasiri Mahboubeh Welfare Organization, Share Kord, Iran aut NATIONALLICENCE 700 1- Falah Masoumeh Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut NATIONALLICENCE 700 1- Nikuei Pooneh Welfare Organization, Bandar Abbas, Iran aut NATIONALLICENCE 700 1- Dehghan Atefeh Welfare Organization, Yazd, Iran aut NATIONALLICENCE 700 1- Sobhani Masoumeh Welfare Organization, Talesh, Iran aut NATIONALLICENCE 700 1- Jamali Payman Welfare Organization, Shahroud, Iran aut NATIONALLICENCE 700 1- Ropers Hans Max Planck Institute for Molecular Genetics, Ihnestr. 73, 14195, Berlin, Germany aut NATIONALLICENCE 700 1- Najmabadi Hossein Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 129/2(2011-02-01), 141-148 0340-6717 129:2<141 2011 129 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer