title: Genetic screening for autosomal recessive nonsyndromic mental retardation in an isolated population in Israel.
abstract: 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 (approximately 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.
authors.affiliation: Department of Medical Genetics, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel. basel@post.tau.ac.il
authors.forename: Lina
authors.initials: L
authors.lastname: Basel-Vanagaite
authors.forename: Ellen
authors.initials: E
authors.lastname: Taub
authors.forename: Gabrielle J
authors.initials: GJ
authors.lastname: Halpern
authors.forename: Valerie
authors.initials: V
authors.lastname: Drasinover
authors.forename: Nurit
authors.initials: N
authors.lastname: Magal
authors.forename: Bella
authors.initials: B
authors.lastname: Davidov
authors.forename: Joël
authors.initials: J
authors.lastname: Zlotogora
authors.forename: Mordechai
authors.initials: M
authors.lastname: Shohat
mesh_terms: D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D005817:Genetic Counseling; D005820:Genetic Testing; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis* / Q000235:genetics; D007557:Israel; D011153:Population / Q000235:genetics; D011247:Pregnancy; D011296:Prenatal Diagnosis
chemical_list: C512283:CC2D1A protein, human; D004268:DNA-Binding Proteins