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Abstract：
Defects in both CYP21A2 and TNXB genes can cause congenital adrenal hyperplasia combined with hypermobility-type Ehlers-Danlos syndrome (EDS), which has recently been named CAH-X syndrome. The purpose of this study is to assess the prevalence of the chimeric TNXA/TNXB gene and clinical symptoms in a Chinese cohort with 21-hydroxylase deficiency (21-OHD).
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.
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.
摘要：
CYP21A2和TNXB基因的缺陷可导致先天性肾上腺增生合并过度活动型Ehlers-Danlos综合征(EDS)。最近被命名为CAH-X综合征。这项研究的目的是评估21-羟化酶缺乏症（21-OHD）中国人群中嵌合TNXA/TNXB基因的患病率和临床症状。
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。
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。
