Homozygosity mapping in 64 Syrian consanguineous families with non-specific intellectual disability reveals 11 novel loci and high heterogeneity

被引：78

作者：

Abou Jamra, Rami ^{[1
,2
]}

Wohlfart, Sigrun ^{[1
]}

Zweier, Markus ^{[1
]}

Uebe, Steffen ^{[1
]}

Priebe, Lutz ^{[2
,3
]}

Ekici, Arif ^{[1
]}

Giesebrecht, Susanne ^{[2
]}

Abboud, Ahmad

Al Khateeb, Mohammed Ayman

Fakher, Mahmoud

Hamdan, Saber

Ismael, Amina

Muhammad, Safia

Noethen, Markus M. ^{[2
]}

Schumacher, Johannes ^{[2
]}

Reis, Andre ^{[1
]}

机构：

[1] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany

[2] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany

[3] Univ Bonn, Life & Brain Ctr, Dept Genom, D-5300 Bonn, Germany

来源：

EUROPEAN JOURNAL OF HUMAN GENETICS | 2011年 / 19卷 / 11期

关键词：

non-specific; mental retardation; microcephaly; epilepsy; MRT; RECESSIVE MENTAL-RETARDATION; LINKAGE ANALYSES; GENE; MUTATION; DEFECT; IDENTIFICATION; EASYLINKAGE; TRAPPC9;

D O I：

10.1038/ejhg.2011.98

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Non-specific intellectual disability of autosomal recessive inheritance (NS-ARID) represents an important fraction of severe cognitive dysfunction disorders. To date, only 10 genes have been identified, and further 24 linked-ARID loci have been reported, as well as others with suggestive linkage. To discover novel genes causing NS-ARID, we undertook genome-wide homozygosity mapping in 64 consanguineous multiplex families of Syrian descent. A total of 11 families revealed unique, significantly linked loci at 4q26-4q28 (MRT17), 6q12-q15 (MRT18), 18p11 (MRT19), 16p12-q12 (MRT20), 11p15 (MRT21), 11p13-q14 (MRT23), 6p12 (MRT24), 12q13-q15 (MRT25), 14q11-q12 (MRT26), 15q23-q26 (MRT27), and 6q26-q27 (MRT28), respectively. Loci ranged between 1.2 and 45.6Mb in length. One family showed linkage to chromosome 8q24.3, and we identified a mutation in TRAPPC9. Our study further highlights the extreme heterogeneity of NS-ARID, and suggests that no major disease gene is to be expected, at least in this study group. Systematic analysis of large numbers of affected families, as presented here, will help discovering the genetic causes of ID. European Journal of Human Genetics (2011) 19, 1161-1166; doi:10.1038/ejhg.2011.98; published online 1 June 2011

引用

页码：1161 / 1166

页数：6

共 29 条

[1]

Bartley J A, 1978, Birth Defects Orig Artic Ser, V14, P127

[2] Exome sequencing reveals a novel mutation for autosomal recessive non-syndromic mental retardation in the TECR gene on chromosome 19p13 [J].

Caliskan, Minal ;

Chong, Jessica X. ;

Uricchio, Lawrence ;

Anderson, Rebecca ;

Chen, Peixian ;

Sougnez, Carrie ;

Garimella, Kiran ;

Gabriel, Stacey B. ;

DePristo, Mark A. ;

Shakir, Khalid ;

Matern, Dietrich ;

Das, Soma ;

Waggoner, Darrel ;

Nicolae, Dan L. ;

Ober, Carole .

HUMAN MOLECULAR GENETICS, 2011, 20 (07) :1285-1289

[3] A defect in the TUSC3 gene is associated with autosomal recessive mental retardation [J].

Garshasbi, Masoud ;

Hadavi, Valeh ;

Habibi, Haleh ;

Kahrizi, Kimia ;

Kariminejad, Roxana ;

Behjati, Farkhondeh ;

Tzschach, Andreas ;

Najmabadi, Hossein ;

Ropers, Hans Hilger ;

Kuss, Andreas Walter .

AMERICAN JOURNAL OF HUMAN GENETICS, 2008, 82 (05) :1158-1164

[4] Allegro version 2 [J].

Gudbjartsson, DF ;

Thorvaldsson, T ;

Kong, A ;

Gunnarsson, G ;

Ingolfsdottir, A .

NATURE GENETICS, 2005, 37 (10) :1015-1016

[5] A mutation in a novel ATP-dependent Lon protease gene in a kindred with mild mental retardation [J].

Higgins, JJ ;

Pucilowska, J ;

Lombardi, RQ ;

Rooney, JP .

NEUROLOGY, 2004, 63 (10) :1927-1931

[6] easyLINKAGE-Plus - automated linkage analyses using large-scale SNP data [J].

Hoffmann, K ;

Lindner, TH .

BIOINFORMATICS, 2005, 21 (17) :3565-3567

[7]

Kruglyak L, 1996, AM J HUM GENET, V58, P1347

[8] Autosomal recessive mental retardation: homozygosity mapping identifies 27 single linkage intervals, at least 14 novel loci and several mutation hotspots [J].

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 ;

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 .

HUMAN GENETICS, 2011, 129 (02) :141-148

[9] easyLINKAGE: a PERL script for easy and automated two-/multi-point linkage analyses [J].

Lindner, TH ;

Hoffmann, K .

BIOINFORMATICS, 2005, 21 (03) :405-407

[10] Identification of Mutations in TRAPPC9, which Encodes the NIK- and IKK-β-Binding Protein, in Nonsyndromic Autosornal-Recessive Mental Retardation [J].

Mir, Asif ;

Kaufman, Liana ;

Noor, Abdul ;

Motazacker, Mahdi M. ;

Jamil, Talal ;

Azam, Matloob ;

Kahrizi, Kimia ;

Rafiq, Muhammad Arshad ;

Weksberg, Rosanna ;

Nasr, Tanveer ;

Naeem, Farooq ;

Tzschach, Andreas ;

Kuss, Andreas W. ;

Ishak, Gisele E. ;

Doherty, Dan ;

Ropers, H. Hilger ;

Barkovich, A. James ;

Najmabadi, Hossein ;

Ayub, Muhammad ;

Vincent, John B. .

AMERICAN JOURNAL OF HUMAN GENETICS, 2009, 85 (06) :909-915

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