TY - JOUR
T1 - Genetic screening for autosomal recessive nonsyndromic mental retardation in an isolated population in Israel
AU - Basel-Vanagaite, Lina
AU - Taub, Ellen
AU - Halpern, Gabrielle J.
AU - Drasinover, Valerie
AU - Magal, Nurit
AU - Davidov, Bella
AU - Zlotogora, Joël
AU - Shohat, Mordechai
N1 - Funding Information:
We are grateful to the families who participated in this study and clinical nurses Hitam, Inshirah, Sylvia, Shiraz and Fatma. This study was funded by the Yeshaya Horovitz grant for Neurogenetics research and the Israeli Science Foundation (grant No 690/04).
Funding Information:
The screening program including genetic counseling and testing was provided free of charge, financed by the Israeli Ministry of Health as part of a program designed towards the prevention of frequent genetic diseases in Israel. All the individuals who were found to be carriers of the G408fsX437 mutation in the CC2D1A gene were offered genetic counseling in which genetic testing of their spouses was recommended. Carrier couples were given genetic counseling and were offered the possibility of free prenatal diagnosis either bychorionic villus sampling (CVS) or amniotic fluid analysis.
PY - 2007/2
Y1 - 2007/2
N2 - Nonsyndromic mental retardation (NSMR) is the diagnosis of exclusion in mentally retarded individuals without additional abnormalities. We have recently identified a protein-truncating mutation, G408fsX437, in the gene CC2D1A on chromosome 19p13.12 in nine consanguineous Israeli Arab families with severe autosomal recessive NSMR, and have developed a comprehensive prevention program among the at-risk population in the village. The subjects tested were healthy women who were invited to undergo the genetic screening test as a part of their routine pregnancy monitoring. One hundred and seventeen subjects reported a family history positive for mental retardation. We tested 524 pregnant or preconceptional women and found 47 carriers (∼1/11), whose spouses were then recommended to undergo testing. We identified eight carrier couples, who were given genetic counseling and offered prenatal diagnosis. Of all the marriages, 28.6% were consanguineous; 16.5% of the total were between first cousins. The high prevalence of the mutation can be explained both by the founder effect owing to the generally high consanguinity rate among the inhabitants of the village, and also because two families with excessive numbers of mentally retarded offspring were unacceptable as marriage partners by the rest of the families. This is the first example of the establishment of a large-scale genetic screening program for autosomal recessive NSMR, which was made possible owing to the high frequency of the specific causative mutation in this isolated population.
AB - Nonsyndromic mental retardation (NSMR) is the diagnosis of exclusion in mentally retarded individuals without additional abnormalities. We have recently identified a protein-truncating mutation, G408fsX437, in the gene CC2D1A on chromosome 19p13.12 in nine consanguineous Israeli Arab families with severe autosomal recessive NSMR, and have developed a comprehensive prevention program among the at-risk population in the village. The subjects tested were healthy women who were invited to undergo the genetic screening test as a part of their routine pregnancy monitoring. One hundred and seventeen subjects reported a family history positive for mental retardation. We tested 524 pregnant or preconceptional women and found 47 carriers (∼1/11), whose spouses were then recommended to undergo testing. We identified eight carrier couples, who were given genetic counseling and offered prenatal diagnosis. Of all the marriages, 28.6% were consanguineous; 16.5% of the total were between first cousins. The high prevalence of the mutation can be explained both by the founder effect owing to the generally high consanguinity rate among the inhabitants of the village, and also because two families with excessive numbers of mentally retarded offspring were unacceptable as marriage partners by the rest of the families. This is the first example of the establishment of a large-scale genetic screening program for autosomal recessive NSMR, which was made possible owing to the high frequency of the specific causative mutation in this isolated population.
UR - http://www.scopus.com/inward/record.url?scp=33846273129&partnerID=8YFLogxK
U2 - 10.1038/sj.ejhg.5201750
DO - 10.1038/sj.ejhg.5201750
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AN - SCOPUS:33846273129
SN - 1018-4813
VL - 15
SP - 250
EP - 253
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 2
ER -