Semerci C N, Demirkan F, Ozdemir M, Biskin E, Akin B, Bagci H, Akarsu N A
Department of Medical Biology, Center for Genetic Diagnosis, School of Medicine, Pamukkale University, Denizli, Turkey.
Clin Genet. 2009 Jul;76(1):85-90. doi: 10.1111/j.1399-0004.2009.01192.x. Epub 2009 Jun 9.
Preaxial polydactyly is a common limb malformation in humans with variable clinical expression. Different types of triphalangeal thumb-preaxial polydactyly phenotypes were mapped to the chromosome 7q36 region. We studied a large Turkish family of 69 individuals, of whom 22 individuals were affected. In all, 11 affected family members were clinically and radiologically evaluated. All affected individuals had a triphalangeal thumb and a preaxial (hypoplastic) extra digit bilaterally, with minimal intrafamilial variation. No feet involvement was observed. Linkage and haplotype analyses using 20 informative meioses confirmed the 7q36 region contained the LIMBR1 gene. Maximum logarithm of the odds (LOD) scores were obtained with DNA markers D7S550 and D7S2423. We have further identified a novel C to T alteration at position 4909 bp in the critical zone of polarizing activity regulatory sequence (ZRS) region, in the intron 5, of the LMBR1 gene. One affected male with homozygous status and no phenotypic difference from affected family members with heterozygous status represented the first homozygote case of the triphalangeal thumb-preaxial polydactyly phenotype.
轴前多指畸形是人类常见的肢体畸形，临床表现多样。不同类型的三指节拇指-轴前多指畸形表型被定位到7号染色体q36区域。我们研究了一个由69人组成的土耳其大家族，其中22人患病。总共对11名患病家庭成员进行了临床和放射学评估。所有患病个体双侧均有三指节拇指和一个轴前（发育不全）额外手指，家族内变异极小。未观察到足部受累情况。使用20个信息性减数分裂进行连锁和单倍型分析证实7q36区域包含LIMBR1基因。使用DNA标记D7S550和D7S2423获得了最大对数优势（LOD）分数。我们进一步在LMBR1基因第5内含子的极化活性调节序列（ZRS）区域的关键区域中，在4909 bp位置鉴定出一个新的C到T改变。一名纯合状态的患病男性与杂合状态的患病家庭成员在表型上无差异，代表了三指节拇指-轴前多指畸形表型的首例纯合子病例。
