Superti-Furga A, Neumann L, Riebel T, Eich G, Steinmann B, Spranger J, Kunze J
Division of Metabolic and Molecular Diseases, University Children's Hospital, Zurich, Switzerland.
J Med Genet. 1999 Aug;36(8):621-4.
We have observed over 25 different mutations in the diastrophic dysplasia sulphate transporter gene (DTDST) in association with the recessive disorders achondrogenesis 1B, atelosteogenesis 2, and diastrophic dysplasia. The c862t (R279W) transition is the most common mutation in non-Finnish patients, but in these disorders it is usually combined with other DTDST mutations. We had not seen a case of homozygosity for c862t (R279W) until we analysed DNA from a 36 year old male with tall-normal stature (180 cm) who asked for genetic counselling for suspected multiple epiphyseal dysplasia. He was treated for club foot and hip dysplasia at birth. Skeletal changes consistent with multiple epiphyseal dysplasia, with the peculiar finding of a double layered patella, were recognised during childhood. Cleft palate, swelling of the ear pinna, and hitch hiker thumb were absent. He was found to be homozygous, and both healthy parents heterozygous, for the R279W mutation in DTDST, and his fibroblasts showed a sulphate incorporation defect typical of DTDST disorders. Counselling was given for a recessive disorder, thereby considerably reducing the probability of affected offspring. Multiple epiphyseal dysplasia is more frequently caused by dominant mutations in the COMP (EDM1, McKusick 132400) and COL9A2 genes (EDM2, McKusick 600204). A few other patients and families with features similar to our proband have been described previously and considered to have autosomal recessive MED (EDM4, McKusick 226900). This observation confirms the existence of this entity and assigns it to the phenotypic spectrum associated with mutations at the DTDST locus.
我们在与隐性疾病软骨发育不全1B型、肢骨发育异常2型和脊柱骨骺发育不良相关的硫酸酯酶转运体基因（DTDST）中观察到超过25种不同的突变。c862t（R279W）转换是非芬兰患者中最常见的突变，但在这些疾病中，它通常与其他DTDST突变同时出现。在分析一名身高正常（180厘米）的36岁男性的DNA之前，我们从未见过c862t（R279W）纯合子病例，该男性因疑似多发性骨骺发育异常而寻求遗传咨询。他出生时因马蹄内翻足和髋关节发育不良接受过治疗。儿童时期发现骨骼变化与多发性骨骺发育异常一致，特别发现有双层髌骨。无腭裂、耳廓肿胀和搭便车拇指。发现他为DTDST基因R279W突变的纯合子，其父母均健康且为杂合子，他的成纤维细胞表现出典型的DTDST疾病硫酸盐摄取缺陷。针对一种隐性疾病提供了咨询，从而大大降低了后代受影响的概率。多发性骨骺发育异常更常见于由COMP（EDM1，McKusick 132400）和COL9A2基因（EDM2，McKusick 600204）中的显性突变引起。先前已经描述了一些其他具有与我们的先证者相似特征的患者和家系，并认为他们患有常染色体隐性遗传性多发性骨骺发育异常（EDM4，McKusick 226900）。这一观察结果证实了该实体的存在，并将其归入与DTDST基因座突变相关的表型谱中。
