假性软骨发育不全一家系临床特征和COMP基因突变分析

Clinical features and COMP gene mutation in a family with a pseudoachondroplasia child

摘要:

假性软骨发育不全（pseudoachondroplasia, PSACH）是较罕见的常染色体显性遗传性脊柱骨骺发育不良疾病。该文分析总结一个5岁2月龄PSACH患儿及其父母的临床资料，对COMP基因的所有19个外显子及其侧翼序列进行PCR扩增和直接测序，并对外显子10进行分子克隆明确突变性质。患儿有手指粗短、弓形腿、短肢侏儒、长骨干骺端增宽和脊柱椎体前突等临床及影像学表现，其COMP基因外显子10检出突变c.1048_1116del（p.Asn350_Asp372del）。患儿父亲外显子10携带同样突变，但缺乏临床表现。结合临床和影像学特征，通过COMP突变分析明确了PSACH诊断。该文报道的COMP基因突变在PSACH中的不穿透现象属于首次报道。

Abstract:

This study aimed to report the clinical characteristics and COMP gene mutation of a family with pseudoachondroplasia (PSACH), a relatively rare spinal and epiphyseal dysplasia that is inherited as an autosomal dominant trait. Clinical information on a 5-year-2-month-old PSACH child and his parents was collected and analyzed. Diagnosis was confirmed by PCR amplification and direct sequencing of all the 19 exons and their flanking sequences of COMP gene, and the mutation was further ascertained by cloning analysis of exon 10. The child presented with short and stubby fingers, bow leg, short limb dwarfism and metaphysic broadening in long bone as well as lumbar lordosis. A mutation c.1048_1116del (p.Asn350_Asp372del) in exon 10, inherited from his father who did not demonstrate any phenotypic feature of PSACH, was detected in the child. PSACH was diagnosed definitively by means of COMP mutation analysis, on the basis of the child's clinical and imaging features. The non-penetrance phenomenon of COMP mutation was described for the first time in PSACH