Basel-Vanagaite L, Alkelai A, Straussberg R, Magal N, Inbar D, Mahajna M, Shohat M
Department of Medical Genetics, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel.
J Med Genet. 2003 Oct;40(10):729-32. doi: 10.1136/jmg.40.10.729.
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.
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.
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.
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.
识别并临床评估四个源于以色列阿拉伯的近亲家庭，这些家庭患有非综合征性智力迟钝（NSMR），共有10名患者和24名未患病个体。
所有家庭都来自同一个小村庄且姓氏相同。排除了这些家庭中该病症与位于3号染色体短臂2区5带至末端及4号染色体长臂2区4带（神经胰蛋白酶基因）上两个已知的常染色体隐性NSMR基因座的关联。
确定了疾病基因与19号染色体短臂1区3带12亚带至1区3带2亚带（标记D19S840在θ = 0.00时Zmax = 7.06）的连锁关系。发现所有患病个体对于标记cen - RFX1 - D19S840 - D19S558 - D19S221 - tel的一个常见单倍型均为纯合子。
结果表明该疾病由所有家庭中一个单一祖先奠基者产生的单一突变引起。重组事件和一个携带疾病的常见单倍型确定了一个关键区域，该区域位于近端的D19S547基因座和远端的D19S1165基因座之间，长度为2.4 Mb。
