Mohammad Mahdi Motazacker

Publications of Mohammad Mahdi Motazacker

• A defect in the ionotropic glutamate receptor 6 gene (GRIK2) is associated with autosomal recessive mental retardation.

  Authors: Mohammad Mahdi Motazacker, Benjamin Rainer Rost, Tim Hucho, Masoud Garshasbi, Kimia Kahrizi, Reinhard Ullmann, Seyedeh Sedigheh Abedini, Sahar Esmaeeli Nieh, Saeid Hosseini Amini, Chandan Goswami, Andreas Tzschach, Lars Riff Jensen, Dietmar Schmitz, Hans-Hilger Ropers, Hossein Najmabadi, Andreas Walter Kuss

  American journal of human genetics. 11/2007; 81(4):792-8.

  Nonsyndromic mental retardation is one of the most important unresolved problems in genetic health care. Autosomal forms are far more common than X-linked forms, but, in contrast to the latter, theyNonsyndromic mental retardation is one of the most important unresolved problems in genetic health care. Autosomal forms are far more common than X-linked forms, but, in contrast to the latter, they are still largely unexplored. Here, we report a complex mutation in the ionotropic glutamate receptor 6 gene (GRIK2, also called "GLUR6") that cosegregates with moderate-to-severe nonsyndromic autosomal recessive mental retardation in a large, consanguineous Iranian family. The predicted gene product lacks the first ligand-binding domain, the adjacent transmembrane domain, and the putative pore loop, suggesting a complete loss of function of the GLU(K6) protein, which is supported by electrophysiological data. This finding provides the first proof that GLU(K6) is indispensable for higher brain functions in humans, and future studies of this and other ionotropic kainate receptors will shed more light on the pathophysiology of mental retardation.

• The Iranian human mutation database.

  Authors: Mohammad Mahdi Motazacker, Elahe Taherzadeh-Fard, Zohreh Husseini, Farkhondeh Behjati, Fatemehsadat Esteghamat, Kimia Kahrizi, Hossein Najmabadi

  Archives of Iranian medicine. 08/2007; 10(3):372-5.

• Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci.

  Authors: Hossein Najmabadi, Mohammad Mahdi Motazacker, Masoud Garshasbi, Kimia Kahrizi, Andreas Tzschach, Wei Chen, Farkhondeh Behjati, Valeh Hadavi, Sahar Esmaeeli Nieh, Seyedeh Sedigheh Abedini [......] Saghar Ghasemi Firouzabadi, Payman Jamali, Masoumeh Falah, Seyed Morteza Seifati, Annette Grüters, Steffen Lenzner, Lars R Jensen, Franz Rüschendorf, Andreas W Kuss, H Hilger Ropers

  Human genetics. 04/2007; 121(1):43-8.

  Autosomal recessive gene defects are arguably the most important, but least studied genetic causes of severe cognitive dysfunction. Homozygosity mapping in 78 consanguineous Iranian families withAutosomal recessive gene defects are arguably the most important, but least studied genetic causes of severe cognitive dysfunction. Homozygosity mapping in 78 consanguineous Iranian families with nonsyndromic autosomal recessive mental retardation (NS-ARMR) has enabled us to determine the chromosomal localization of at least 8 novel gene loci for this condition. Our data suggest that in the Iranian population NS-ARMR is very heterogeneous, and they argue against the existence of frequent gene defects that account for more than a few percent of the cases.

• SNP array-based homozygosity mapping reveals MCPH1 deletion in family with autosomal recessive mental retardation and mild microcephaly.

  Authors: Masoud Garshasbi, Mohammad Mahdi Motazacker, Kimia Kahrizi, Farkhondeh Behjati, Seyedeh Sedigheh Abedini, Sahar Esmaeeli Nieh, Saghar Ghasemi Firouzabadi, Christian Becker, Franz Rüschendorf, Peter Nürnberg, Andreas Tzschach, Reza Vazifehmand, Fikret Erdogan, Reinhard Ullmann, Steffen Lenzner, Andreas W Kuss, H Hilger Ropers, Hossein Najmabadi

  Human genetics. 03/2006; 118(6):708-15.

  Very little is known about the molecular basis of autosomal recessive MR (ARMR) because in developed countries, small family sizes preclude mapping and identification of the relevant gene defects. WeVery little is known about the molecular basis of autosomal recessive MR (ARMR) because in developed countries, small family sizes preclude mapping and identification of the relevant gene defects. We therefore chose to investigate genetic causes of ARMR in large consanguineous Iranian families. This study reports on a family with six mentally retarded members. Array-based homozygosity mapping and high-resolution microarray-based comparative genomic hybridization (array CGH) revealed a deletion of approximately 150-200 kb, encompassing the promoter and the first six exons of the MCPH1 gene, one out of four genes that have been previously implicated in ARMR with microcephaly. Reexamination of affected individuals revealed a high proportion of prematurely condensed chromosomes, which is a hallmark of this condition, but in spite of the severity of the mutation, all patients showed only borderline to mild microcephaly. Therefore the phenotypic spectrum of MCPH1 mutations may be wider than previously assumed, with ARMR being the only consistent clinical finding.