NDLI: Autosomal recessive mental retardation: homozygosity mapping identifies 27 single linkage intervals, at least 14 novel loci and several mutation hotspots

Content Provider	Springer Nature Link
Author	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
Copyright Year	2010
Abstract	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.
Starting Page	141
Ending Page	148
Page Count	8
File Format	PDF
ISSN	03406717
Journal	Human Genetics
Volume Number	129
Issue Number	2
e-ISSN	14321203
Language	English
Publisher	Springer-Verlag
Publisher Date	2010-11-10
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Human Genetics Metabolic Diseases Gene Function Molecular Medicine
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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

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

Mapping of a novel autosomal recessive hypotrichosis locus on chromosome 10q11.23–22.3

Autosomal Recessive Alzheimer’s disease (arAD): homozygosity mapping of genomic regions containing arAD loci

Molecular genetics (2009).

Mutation of ATF6 causes autosomal recessive achromatopsia

Combination of Linkage Mapping and Microarray-Expression Analysis Identifies NF-κB Signaling Defect as a Cause of Autosomal-Recessive Mental Retardation

STIL mutation causes autosomal recessive microcephalic lobar holoprosencephaly

A Novel Genetic Study of Chinese Families with Autosomal Recessive

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

Similar Documents

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

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

Mapping of a novel autosomal recessive hypotrichosis locus on chromosome 10q11.23–22.3

Autosomal Recessive Alzheimer’s disease (arAD): homozygosity mapping of genomic regions containing arAD loci

Molecular genetics (2009).

Mutation of ATF6 causes autosomal recessive achromatopsia

Combination of Linkage Mapping and Microarray-Expression Analysis Identifies NF-κB Signaling Defect as a Cause of Autosomal-Recessive Mental Retardation

STIL mutation causes autosomal recessive microcephalic lobar holoprosencephaly

A Novel Genetic Study of Chinese Families with Autosomal Recessive

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