ORIGINAL ARTICLE

Mapping of a new locus for autosomal recessive non-syndromic mental retardation in the chromosomal region 19p13.12-p13.2: further genetic heterogeneity

L Basel-Vanagaite^1,2,*, A Alkelai^3,*, R Straussberg^2,4, N Magal^3,4, D Inbar⁵, M Mahajna⁵, M Shohat^1,4

¹ Department of Medical Genetics, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel
² Neurogenetics Clinic and Department of Pediatrics, Schneider Children’s Medical Center of Israel, Petah Tikva, Israel
³ Felsenstein Medical Research Center, Petah Tikva, Israel
⁴ Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
⁵ Neuropediatrics Unit, Schneider Children’s Medical Center of Israel, Petah Tikva, Israel

Correspondence to:
Correspondence to:
L Basel-Vanagaite
Medical Genetics Department, Rabin Medical Center, Beilinson Campus, Petah Tikva 49100, Israel; basel{at}post.tau.ac.il

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.

Participants and 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.

Keywords: homozygosity mapping; nonsyndromic mental retardation; autosomal recessive

Abbreviations: MR, mental retardation; NSMR, nonsyndromic mental retardation; IQ, intelligence quotient; PCR, polymerase chain reaction

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