A total of 424 patients with 21-OHD who were genetically diagnosed were recruited for this study. Multiplex ligation-dependent probe amplification and sequencing were used to identify the CAH-X genotype. Clinical features of joints, skin, and other systems were evaluated in 125 patients.
Ninety-four of the 424 patients had a deletion on at least 1 allele of CYP21A2 and 59 of them harbored the heterozygotic TNXA/TNXB chimera. Frequencies of CAH-X CH-1, CH-2, and CH-3 were 8.2%, 3.1%, and 2.6%, respectively. The incidences of clinical features of EDS were 71.0% and 26.6% in patients with the chimeric TNXA/TNXB genes or without (P < .001). There were statistically significant differences in manifestations among articular (P < .001 in generalized hypermobility) and dermatologic features (P < .001 in hyperextensible skin, P = .015 in velvety skin and P = .033 in poor wound healing). The prevalence of generalized hypermobility was more common in CAH-X CH-2 or CH-3 than CH-1 patients (60% vs 20%, P = .028).
In summary, about 14% of patients with 21-OHD may have chimeric TNXA/TNXB gene mutations in our study and most of them showed EDS-related clinical symptoms. The correlation between CAH-X genotypes and clinical features in connective tissue, like joint or skin, needs to be further investigated.
本研究共招募了424例经基因诊断的21-OHD患者。多重连接依赖性探针扩增和测序用于鉴定CAH-X基因型。关节的临床特征,皮肤,和其他系统在125例患者中进行了评估。
424名患者中有94名患者在CYP21A2的至少1个等位基因上缺失,其中59名患者具有杂合子TNXA/TNXB嵌合体。CAH-XCH-1,CH-2和CH-3的频率为8.2%,3.1%,和2.6%,分别。在具有或不具有嵌合TNXA/TNXB基因的患者中,EDS的临床特征发生率分别为71.0%和26.6%(P<0.001)。有统计学上显著差异的表现之间的关节(P<.001在全身过度活动)和皮肤病学特征(P<.001在过度伸展的皮肤,在柔软的皮肤中P=.015,在伤口愈合不良中P=.033)。与CH-1患者相比,CAH-XCH-2或CH-3患者的广泛性过度活动率更常见(60%vs20%,P=.028)。
总之,在我们的研究中,约有14%的21-OHD患者可能存在嵌合TNXA/TNXB基因突变,其中大多数患者表现出与EDS相关的临床症状.CAH-X基因型与结缔组织临床特征的相关性,像关节或皮肤,需要进一步调查。