Raas-Rothschild A, Manouvrier S, Gonzales M, Farriaux J P, Lyonnet S, Munnich A
Département de Génétique, INSERM U-393, Hôpital des Enfants-Malades, Paris, France.
J Med Genet. 1996 Dec;33(12):996-1001. doi: 10.1136/jmg.33.12.996.
Split hand-split foot malformation (SHFM) is a genetically heterogeneous limb developmental defect characterised by the absence of digital rays and syndactyly of the remaining digits. Three disease loci have recently been mapped to chromosomes 7q21 (SHFM1), Xq26 (SHFM2), and 10q25 respectively (SHFM3). We report the mapping of SHFM3 to chromosome 10q25 in two large SHFM families of French ancestry (Zmax for the combined families = 6.62 at theta = 0 for marker AFM249wc5 at locus D10S222). Two recombinant events reduced the critical region to a 9 cM interval (D10S1709-D10S1663) encompassing several candidate genes including a paired box gene PAX2 (Zmax = 5.35 at theta = 0). The fibroblast growth factor 8 (FGF 8), the retinol binding protein (RBP4), the zinc finger protein (ZNF32), and the homeobox genes HMX2 and HOX11 are also good candidates by both their position and their function.
裂手裂足畸形（SHFM）是一种具有遗传异质性的肢体发育缺陷，其特征为指骨缺失和剩余手指并指。最近已分别将三个疾病位点定位到7号染色体q21区域（SHFM1）、X染色体q26区域（SHFM2）和10号染色体q25区域（SHFM3）。我们报告了在两个具有法国血统的大型SHFM家系中将SHFM3定位到10号染色体q25区域（在基因座D10S222处标记AFM249wc5的θ=0时，两个家系合并后的Zmax = 6.62）。两次重组事件将关键区域缩小到一个9厘摩的区间（D10S1709 - D10S1663），该区间包含几个候选基因，其中包括一个配对盒基因PAX2（在θ=0时Zmax = 5.35）。成纤维细胞生长因子8（FGF 8）、视黄醇结合蛋白（RBP4）、锌指蛋白（ZNF32）以及同源盒基因HMX2和HOX11，因其位置和功能，也是很好的候选基因。
