Faivre Laurence, Le Merrer Martine, Zerres Klaus, Ben Hariz Mongi, Scheffer Déborah, Young Ian D, Maroteaux Pierre, Munnich Arnold, Cormier-Daire Valérie
Département de Génétique et INSERM U393, Hôpital Necker Enfants Malades, 149 rue de Sévres, 75015 Paris, France.
Am J Med Genet A. 2004 Jul 1;128A(1):29-32. doi: 10.1002/ajmg.a.30042.
Desbuquois dysplasia is a rare chondrodysplasia of autosomal recessive inheritance characterized by short stature, joint laxity, facial anomalies, a "Swedish key" appearance of the proximal femur, and advanced carpal and tarsal bone age. Patients with Desbuquois dysplasia can be divided in two groups, depending on whether hand changes include an extra ossification center distal to the second metacarpal and whether phalangeal dislocations are present or absent. We have recently reported linkage of a Desbuquois dysplasia gene to 17q25.3 in a group of patients with typical hand abnormalities. Here, we report on the exclusion of the 17q25.3 locus in three inbred Desbuquois families originated from Turkey, Asia, and Morocco without typical hand abnormalities. Microsatellite DNA markers from the 17q25.3 region were used at an average spacing of 2 cM, and the three affected individuals from families 1 to 3 were heterozygous for the 17q25.3 region. These results allow us to exclude this region as the locus in Desbuquois families with no hand anomalies and demonstrate genetic heterogeneity. Ongoing studies will hopefully lead to the identification of the responsible genes.
德布凯发育不全是一种罕见的常染色体隐性遗传软骨发育不良，其特征为身材矮小、关节松弛、面部异常、股骨近端呈“瑞典钥匙”外观以及腕骨和跗骨骨龄提前。根据手部变化是否包括第二掌骨远端的额外骨化中心以及是否存在指骨脱位，德布凯发育不全患者可分为两组。我们最近报道了一组具有典型手部异常的患者中，一个德布凯发育不全基因与17q25.3连锁。在此，我们报告在来自土耳其、亚洲和摩洛哥的三个近亲德布凯家族中排除17q25.3位点，这些家族无典型手部异常。使用来自17q25.3区域的微卫星DNA标记，平均间距为2厘摩，家族1至3中的三名受影响个体在17q25.3区域为杂合子。这些结果使我们能够排除该区域作为无手部异常的德布凯家族的致病位点，并证明了遗传异质性。正在进行的研究有望导致鉴定出致病基因。
