Autosomal recessive multiple epiphyseal dysplasia with homozygosity for C653S in the DTDST gene:: Double-layer patella as a reliable sign
Autosomal recessive multiple epiphyseal dysplasia with homozygosity for C653S in the DTDST gene:: Double-layer patella as a reliable sign
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DOI：
10.1002/ajmg.a.20282
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发表时间：
2003-10-15
影响因子：
2
通讯作者：
Cole, WG
中科院分区：
文献类型：
--
作者：
Mäkitie, O;Savarirayan, R;Cole, WG
毁坏性发育不良硫酸盐转运蛋白 (DTDST) 基因突变会导致一系列骨骼发育不良，其中包括致死性（1B 型软骨发育不良和 2 型软骨发育不良）和非致死性病症（毁坏性发育不良和隐性多发性骨骺发育不良 (rMED)）。最常见的突变是 R279W，它在纯合状态下会导致 rMED，伴有双侧马蹄内翻足、MED 和“双层”髌骨。我们描述了三名由先前未报告的 DTDST 基因纯合突变引起的 rMED 患者。这三名患者（来自两个家庭）都是健康的非近亲父母所生。所有儿童均在儿童早期出现髋关节发育不良的症状，其中两人曾出现过复发性髌骨脱位。其中两人分别在 13 岁和 14 岁时接受了双侧全髋关节置换术。脚、外耳和上颚正常。所有病例的身材均正常。 X光片显示股骨头发育不良，轻度全身骨骺发育不良，髌骨骨化异常，手足正常。基因组 DNA 的直接序列分析表明，所有患者的 DTDST 基因均出现纯合 1984T>A (C653S) 变化。临床正常的父母的这种变化是杂合的。这是对 DTDST 基因纯合 C653S 突变的首次描述。髋关节发育不良和髌骨活动过度主导着其他轻微的表型。这些患者进一步扩大了 DTD 骨骼发育不良家族的致病突变范围。 (C) 2003 Wiley-Liss, Inc.
Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene result in a family of skeletal dysplasias, which comprise lethal (achondrogenesis type 1B and atelosteogenesis type 2) and non-lethal conditions (diastrophic dysplasia and recessive multiple epiphyseal dysplasia (rMED)). The most frequent mutation is R279W, which in a homozygous state results in rMED with bilateral clubfoot, MED, and "double layered" patella. We describe three patients with rMED caused by a previously unreported homozygous mutation in the DTDST gene. The three patients (from two families) were born to healthy, non-consanguineous parents. All developed signs of hip dysplasia in early childhood and two had episodes of recurrent patella dislocation. Two underwent bilateral total hip replacements at ages 13 and 14 years. The feet, external ears, and palate were normal. Stature was normal in all cases. Radiographs showed dysplastic femoral heads, mild generalized epiphyseal dysplasia, abnormal patella ossification, and normal hands and feet. Direct sequence analysis of genomic DNA demonstrated a homozygous 1984T>A (C653S) change in the DTDST gene in all patients. The clinically normal parents were heterozygous for the change. This is the first description of a homozygous C653S mutation of the DTDST gene. Hip dysplasia and patella hypermobility dominates the otherwise mild phenotype. These patients further expand the range of causative mutations in the DTD skeletal dysplasia family. (C) 2003 Wiley-Liss, Inc.