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

• Published in: Journal of medical genetics Vol. 40; no. 10; pp. 729 - 732
• Main Authors: Basel-Vanagaite, L, Alkelai, A, Straussberg, R, Magal, N, Inbar, D, Mahajna, M, Shohat, M
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01-10-2003; BMJ Publishing Group LTD; BMJ Group
• Subjects: Ataxia; autosomal recessive; Brain research; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 19; Consanguinity; Deoxyribonucleic acid; DNA; Female; Gene expression; Gene loci; Genetic Linkage; Genetic Predisposition to Disease; Genetic Variation; Genomes; Haplotypes; homozygosity mapping; Homozygote; Humans; Intellectual disabilities; Intellectual Disability - diagnosis; Intellectual Disability - genetics; intelligence quotient; Kinases; Male; mental retardation; nonsyndromic mental retardation; NSMR; Original; PCR; Pedigree; polymerase chain reaction; Proteins
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.40.10.729

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.