BACKGROUND Acromicric dysplasia(AD)is a rare skeletal dysplasia.Its incidence is<1/1000000,and only approximately 60 cases are reported worldwide.It is a disease characterized by severe short stature,short hands an...BACKGROUND Acromicric dysplasia(AD)is a rare skeletal dysplasia.Its incidence is<1/1000000,and only approximately 60 cases are reported worldwide.It is a disease characterized by severe short stature,short hands and feet,facial abnormalities,normal intelligence,and bone abnormalities.Unlike other skeletal dysplasia,AD has a mild clinical phenotype,mainly characterized by short stature.Extensive endocrine examination has not revealed a potential cause.The clinical effect of growth hormone therapy is still uncertain.CASE SUMMARY We report a clinical phenotype of AD associated with mutations in the fibrillin 1(FBN1)(OMIM 102370)gene c.5183C>T(p.Ala1728Val)in three people from a Chinese family.A 4-year-old member of the family first visited the hospital because of slow growth and short stature for 2 years,but no abnormalities were found after a series of laboratory tests,echocardiography,pituitary magnetic resonance imaging,and ophthalmological examination.Recombinant human growth hormone(rhGH)was used to treat the patient for>5 years.The efficacy of rhGH was apparent in the first year of treatment;the height increased from-3.64 standard deviation score(SDS)to-2.88 SDS,while the efficacy weakened from the second year.However,long-term follow-up is required to clarify the efficacy of rhGH.CONCLUSION FBN1-related AD has genetic heterogeneity and/or clinical variability,which brings challenges to the evaluation of clinical treatment.rhGH is effective for treatment of AD,but long-term follow-up is needed to clarify the effect.展开更多
目的:探讨原纤维蛋白-1(Fibrillin-1)、纤维蛋白-5(Fibulin-5)及类赖氨酰氧化酶-1(lysyl-oxidase-1,LOXL-1)在盆底器官脱垂(pelvic organ prolapse,POP)患者阴道前壁组织中的表达及意义。方法:选取2018年1月至2019年2月在海南省妇幼保...目的:探讨原纤维蛋白-1(Fibrillin-1)、纤维蛋白-5(Fibulin-5)及类赖氨酰氧化酶-1(lysyl-oxidase-1,LOXL-1)在盆底器官脱垂(pelvic organ prolapse,POP)患者阴道前壁组织中的表达及意义。方法:选取2018年1月至2019年2月在海南省妇幼保健院手术治疗的盆底器官脱垂患者108例作为观察组,其中POP-QⅡ度患者67例,POP-QⅢ度患者41例;同时选取因宫颈上皮内瘤变或妇科良性病变行子宫全切术患者92例作为对照组。术中均取阴道前壁组织,采用免疫组化法检测组织Fibrillin-1、Fibulin-5、LOXL-1蛋白表达情况,RT-PCR定量检测Fibrillin-1、Fibulin-5、LOXL-1 m RNA在组织标本中的表达水平,并进行对比分析。同时分析盆底器官脱垂患者阴道前壁组织中Fibrillin-1、Fibulin-5、LOXL-1表达的关系。结果:观察组阴道组织Fibrillin-1、Fibulin-5、LOXL-1蛋白阳性表达率及mRNA的相对表达量均明显低于对照组,经卡方检验及t检验,差异均有统计学意义(均P=0.000);POP-QⅡ度患者阴道前壁组织Fibrillin-1、Fibulin-5、LOXL-1蛋白阳性表达率及mRNA的相对表达量均高于POP-QⅢ度患者,经卡方检验及t检验,差异均有统计学意义(P=0.031,P=0.017,P=0.008,P=0.000,P=0.000,P=0.013)。POP患者阴道前壁组织Fibrillin-1与Fibulin-5、Fibrillin-1与LOXL-1、Fibulin-5与LOXL-1蛋白表达及mRNA的相对表达量经Spearman秩相关及Pearson相关分析均呈显著正相关(均P=0.000)。结论:盆底器官脱垂患者阴道组织Fibrillin-1、Fibulin-5及LOXL-1表达降低,且均与脱垂程度密切相关,三者间通过交联作用而呈显著相关性。展开更多
Objective To describe two Chinese patients with severe forms of Marfan syndrome and to report findings of mutational analysis of the fibrillin-1 (FBN1) gene.Methods Two Chinese patients were studied, one suffering fro...Objective To describe two Chinese patients with severe forms of Marfan syndrome and to report findings of mutational analysis of the fibrillin-1 (FBN1) gene.Methods Two Chinese patients were studied, one suffering from Marfan syndrome of infantile onset and the other of neonatal onset. Their clinical features were described. Mutational analysis of the FBN1 gene was performed using polymerase chain reaction (PCR) technique and direct sequencing of exons 23 - 32,where the mutational hotspots for severe forms of Marfan syndrome are located.Results Two missense mutations were successfully identified, a G3037A transition and an A3083T transversion, the latter being an unreported mutation.Conclusion Taking advantage of the clustering phenomenon of mutations in severe forms of Marfan syndrome, one can identify FBN1 mutations in these patients by first screening the mutational hotspots,thus reducing the effort that would otherwise be much greater because of the size of the gene.展开更多
文摘BACKGROUND Acromicric dysplasia(AD)is a rare skeletal dysplasia.Its incidence is<1/1000000,and only approximately 60 cases are reported worldwide.It is a disease characterized by severe short stature,short hands and feet,facial abnormalities,normal intelligence,and bone abnormalities.Unlike other skeletal dysplasia,AD has a mild clinical phenotype,mainly characterized by short stature.Extensive endocrine examination has not revealed a potential cause.The clinical effect of growth hormone therapy is still uncertain.CASE SUMMARY We report a clinical phenotype of AD associated with mutations in the fibrillin 1(FBN1)(OMIM 102370)gene c.5183C>T(p.Ala1728Val)in three people from a Chinese family.A 4-year-old member of the family first visited the hospital because of slow growth and short stature for 2 years,but no abnormalities were found after a series of laboratory tests,echocardiography,pituitary magnetic resonance imaging,and ophthalmological examination.Recombinant human growth hormone(rhGH)was used to treat the patient for>5 years.The efficacy of rhGH was apparent in the first year of treatment;the height increased from-3.64 standard deviation score(SDS)to-2.88 SDS,while the efficacy weakened from the second year.However,long-term follow-up is required to clarify the efficacy of rhGH.CONCLUSION FBN1-related AD has genetic heterogeneity and/or clinical variability,which brings challenges to the evaluation of clinical treatment.rhGH is effective for treatment of AD,but long-term follow-up is needed to clarify the effect.
文摘目的:探讨原纤维蛋白-1(Fibrillin-1)、纤维蛋白-5(Fibulin-5)及类赖氨酰氧化酶-1(lysyl-oxidase-1,LOXL-1)在盆底器官脱垂(pelvic organ prolapse,POP)患者阴道前壁组织中的表达及意义。方法:选取2018年1月至2019年2月在海南省妇幼保健院手术治疗的盆底器官脱垂患者108例作为观察组,其中POP-QⅡ度患者67例,POP-QⅢ度患者41例;同时选取因宫颈上皮内瘤变或妇科良性病变行子宫全切术患者92例作为对照组。术中均取阴道前壁组织,采用免疫组化法检测组织Fibrillin-1、Fibulin-5、LOXL-1蛋白表达情况,RT-PCR定量检测Fibrillin-1、Fibulin-5、LOXL-1 m RNA在组织标本中的表达水平,并进行对比分析。同时分析盆底器官脱垂患者阴道前壁组织中Fibrillin-1、Fibulin-5、LOXL-1表达的关系。结果:观察组阴道组织Fibrillin-1、Fibulin-5、LOXL-1蛋白阳性表达率及mRNA的相对表达量均明显低于对照组,经卡方检验及t检验,差异均有统计学意义(均P=0.000);POP-QⅡ度患者阴道前壁组织Fibrillin-1、Fibulin-5、LOXL-1蛋白阳性表达率及mRNA的相对表达量均高于POP-QⅢ度患者,经卡方检验及t检验,差异均有统计学意义(P=0.031,P=0.017,P=0.008,P=0.000,P=0.000,P=0.013)。POP患者阴道前壁组织Fibrillin-1与Fibulin-5、Fibrillin-1与LOXL-1、Fibulin-5与LOXL-1蛋白表达及mRNA的相对表达量经Spearman秩相关及Pearson相关分析均呈显著正相关(均P=0.000)。结论:盆底器官脱垂患者阴道组织Fibrillin-1、Fibulin-5及LOXL-1表达降低,且均与脱垂程度密切相关,三者间通过交联作用而呈显著相关性。
文摘Objective To describe two Chinese patients with severe forms of Marfan syndrome and to report findings of mutational analysis of the fibrillin-1 (FBN1) gene.Methods Two Chinese patients were studied, one suffering from Marfan syndrome of infantile onset and the other of neonatal onset. Their clinical features were described. Mutational analysis of the FBN1 gene was performed using polymerase chain reaction (PCR) technique and direct sequencing of exons 23 - 32,where the mutational hotspots for severe forms of Marfan syndrome are located.Results Two missense mutations were successfully identified, a G3037A transition and an A3083T transversion, the latter being an unreported mutation.Conclusion Taking advantage of the clustering phenomenon of mutations in severe forms of Marfan syndrome, one can identify FBN1 mutations in these patients by first screening the mutational hotspots,thus reducing the effort that would otherwise be much greater because of the size of the gene.
