Mapping of a new locus for autosomal recessive non-syndromic mental retardation in the chromosomal region 19p13.12-p13.2: further genetic heterogeneity.
OBJECTIVE
To identify and clinically evaluate four consanguineous families of Israeli Arab origin with non-syndromic mental retardation (NSMR), comprising a total of 10 affected and 24 unaffected individuals.


METHODS
All the families originated from the same small village and had the same family name. Association of the condition in these families with the two known autosomal recessive NSMR loci on chromosomes 3p25-pter and 4q24 (neurotrypsin gene) was excluded.


RESULTS
Linkage of the disease gene to chromosome 19p13.12-p13.2(Zmax = 7.06 at theta = 0.00) for the marker D19S840 was established. All the affected individuals were found to be homozygous for a common haplotype for the markers cen-RFX1-D19S840-D19S558-D19S221-tel.


CONCLUSIONS
The results suggest that the disease is caused by a single mutation derived from a single ancestral founder in all the families. Recombination events and a common disease bearing haplotype defined a critical region of 2.4 Mb, between the loci D19S547 proximally and D19S1165 distally.
Department of Medical Genetics, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel. basel@post.tau.ac.il
L
L
Basel-Vanagaite
A
A
Alkelai
R
R
Straussberg
N
N
Magal
D
D
Inbar
M
M
Mahajna
M
M
Shohat
D002874:Chromosome Mapping; D002888:Chromosomes, Human, Pair 19; D003241:Consanguinity; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D010375:Pedigree