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          Institute: MPI für molekulare Genetik     Collection: Department of Human Molecular Genetics     Display Documents

ID: 533429.0, MPI für molekulare Genetik / Department of Human Molecular Genetics
Autosomal recessive mental retardation: homozygosity mapping identifies 27 single linkage intervals, at least 14 nvel loci and several mutation hotspots
Authors:Kuss, Andreas Walter; Garshasbi, Masoud; Kahrizi, Kimia; Tzschach, Andreas; Behjati, Farkhondeh; Darvish, Hossein; Abbasi-Moheb, Lia; Puettmann, Lucia; Zecha, Agnes; Weißmann, Robert; Hu, Hao; Mohseni, Marzieh; Abedini, Seyedeh Sedigheh; Rajab, Anna; Hertzberg, Christoph; Wieczorek, Dagmar; Ullmann, Reinhard; Saghar Ghasemi-Firouzabadi, Saghar; Banihashemi, Susan; Arzhangi, Sanaz; Hadavi, Valeh; Bahrami-Monajemi, Gholamreza; Kasiri, Mahboubeh; Falah, Masoumeh; Nikuei, Pooneh; Dehghan, Atefeh; Sobhani, Masoumeh; Jamali, Payman; Ropers, Hans-Hilger; Najmabadi, Hossein
Date of Publication (YYYY-MM-DD):2010-11-09
Title of Journal:Human Genetics
Journal Abbrev.:Hum. Genet.
Issue / Number:2
Start Page:141
End Page:148
Copyright: Springer-Verlag 2010
Review Status:not specified
Audience:Experts Only
Abstract / Description: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.
Comment of the Author/
Electronic supplementary material The online version of this
article (doi:10.1007/s00439-010-0907-3) contains supplementary
material, which is available to authorized users.
External Publication Status:published
Document Type:Article
Communicated by:Hans-Hilger Ropers
Affiliations:MPI für molekulare Genetik
External Affiliations:1.Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran;
2.Genetics Unit, Ministry of Health, Directorate General of Health Affairs, Royal Hospital, Muscat, Sultanate of Oman;
3.Vivantes Klinikum Neukölln, Berlin, Germany;
4.Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany;
4.Welfare Organization, Share Kord, Iran;
5.Welfare Organization, Bandar Abbas, Iran;
6.Welfare Organization, Yazd, Iran;
7.Welfare Organization, Talesh, Iran;
8.Welfare Organization, Shahroud, Iran;
9.Kariminejad-Najmabadi Pathology and Genetics Center, Tehran, Iran.
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