本文报道了1例罕见的额骨干骺端发育不良2型成年男性患者,其临床表现为眶上嵴突出、宽鼻梁、小下颌,同时合并多发颞骨骨瘤、手足畸形、脊柱侧弯、感音神经性聋,基因学检测发现MAP3K7基因的杂合错义变异c.1454C>T/p.P485L。对该患者...本文报道了1例罕见的额骨干骺端发育不良2型成年男性患者,其临床表现为眶上嵴突出、宽鼻梁、小下颌,同时合并多发颞骨骨瘤、手足畸形、脊柱侧弯、感音神经性聋,基因学检测发现MAP3K7基因的杂合错义变异c.1454C>T/p.P485L。对该患者进行了人工耳蜗植入、颞骨骨瘤切除及外耳道重建术,患者生活质量得到了明显提升,术后听觉行为分级标准(categories of auditory performance,CAP)达5级,即不借助唇读可理解常用短语。展开更多
A couple with a proband child of GJB2(encoding the gap junction protein connexin 26)-associated hearing impairment and a previous pregnancy miscarriage sought for a reproductive solution to bear a healthy child. Our s...A couple with a proband child of GJB2(encoding the gap junction protein connexin 26)-associated hearing impairment and a previous pregnancy miscarriage sought for a reproductive solution to bear a healthy child. Our study aimed to develop a customized preconception-to-neonate care trajectory to fulfill this clinical demand by integrating preimplantation genetic diagnosis(PGD), noninvasive prenatal testing(NIPT), and noninvasive prenatal diagnosis(NIPD) into the strategy. Auditory and genetic diagnosis of the proband child was carried out to identify the disease causative mutations. The couple then received in-vitro-fertilization treatment, and eight embryos were obtained for day 5 biopsy. PGD was performed by short-tandem-repeat linkage analysis and Sanger sequencing of GJB2 gene. Transfer of a GJB2 c.235del C heterozygous embryo resulted in a singleton pregnancy. At the 13 th week of gestation, genomic DNA(g DNA) from the trio family and cell-free DNA(cf DNA) from maternal plasma were obtained for assessment of fetal chromosomal aneuploidy and GJB2 mutations. NIPT and NIPD showed the absence of chromosomal aneuploidy and GJB2-associated disease in the fetus, which was later confirmed by invasive procedures and postnatal genetic/auditory diagnosis. This strategy successfully prevented the transmission of hearing impairment in the newborn, thus providing a valuable experience in reproductive management of similar cases and potentially other monogenic disorders.展开更多
Background:Sudden sensorineural hearing loss(SSHL)refers to the sudden occurrence of unexplained sensorineural hearing loss.The present study showed that different systemic diseases had different influence on the occu...Background:Sudden sensorineural hearing loss(SSHL)refers to the sudden occurrence of unexplained sensorineural hearing loss.The present study showed that different systemic diseases had different influence on the occurrence and hearing outcome of SSHL.Thyroid hormone is one of the important factors for the development of fetal ear and auditory function.However,the distribution of thyroid dysfunction in SSHL patients and the effect of thyroid dysfunction on the occurrence and hearing outcome of SSHL has not been studied.Methods:In this study,a retrospective analysis had been done in 676 patients with SSHL.We had described the distribution of thyroid function in patients with SSHL in detail,and by the statistical method,analyzed the relationship between the hearing outcome and thyroid dysfunction,respectively.Results:In all patients,24.41%(165/676)had abnormal thyroid function testing results.The onset age of SSHL in FT3 abnormal group(including low and high group)was younger than that in normal FT3 group.Recovery group had more patients with lower-than-normal T3 level as compared to non-recovery patients.Significant associations between T3 levels and hearing outcome were observed in the subgroup with longer time elapse between symptom onset and treatment(≥14 d).Conclusion:The incidence of thyroid dysfunction in SSHL is significantly higher than in the general population.There was obvious relationship between T3 and FT3 item of thyroid dysfunction and the onset time and hearing outcome of SSHL,which indicated that T3 or FT3 indicator may be one of the affecting factors for the SSHL.Early screening and diagnosis of thyroid dysfunction,especial T3 level,may help to evaluate the prognosis in SSHL patients.展开更多
文摘本文报道了1例罕见的额骨干骺端发育不良2型成年男性患者,其临床表现为眶上嵴突出、宽鼻梁、小下颌,同时合并多发颞骨骨瘤、手足畸形、脊柱侧弯、感音神经性聋,基因学检测发现MAP3K7基因的杂合错义变异c.1454C>T/p.P485L。对该患者进行了人工耳蜗植入、颞骨骨瘤切除及外耳道重建术,患者生活质量得到了明显提升,术后听觉行为分级标准(categories of auditory performance,CAP)达5级,即不借助唇读可理解常用短语。
基金supported by the National Program on Key Basic Research Project(2014CB943001 and 2012CB944700)the National Natural Science Foundation of China(81120108009 and 81530032)+3 种基金the National Health and Family Planning Commission of the People's Republic of China(201402004)Science and Technology Plan of Guangdong Province(2013B022000005)Guangdong Enterprise Key Laboratory of Human Disease Genomics(2011A060906007)Shenzhen Engineering Laboratory for Birth Defects Screening([2011]861)
文摘A couple with a proband child of GJB2(encoding the gap junction protein connexin 26)-associated hearing impairment and a previous pregnancy miscarriage sought for a reproductive solution to bear a healthy child. Our study aimed to develop a customized preconception-to-neonate care trajectory to fulfill this clinical demand by integrating preimplantation genetic diagnosis(PGD), noninvasive prenatal testing(NIPT), and noninvasive prenatal diagnosis(NIPD) into the strategy. Auditory and genetic diagnosis of the proband child was carried out to identify the disease causative mutations. The couple then received in-vitro-fertilization treatment, and eight embryos were obtained for day 5 biopsy. PGD was performed by short-tandem-repeat linkage analysis and Sanger sequencing of GJB2 gene. Transfer of a GJB2 c.235del C heterozygous embryo resulted in a singleton pregnancy. At the 13 th week of gestation, genomic DNA(g DNA) from the trio family and cell-free DNA(cf DNA) from maternal plasma were obtained for assessment of fetal chromosomal aneuploidy and GJB2 mutations. NIPT and NIPD showed the absence of chromosomal aneuploidy and GJB2-associated disease in the fetus, which was later confirmed by invasive procedures and postnatal genetic/auditory diagnosis. This strategy successfully prevented the transmission of hearing impairment in the newborn, thus providing a valuable experience in reproductive management of similar cases and potentially other monogenic disorders.
基金This work was supported by National Natural Science Foundation of China,China(81530032,81500794 and 81370021)Military Medical Youth Project of PLA General Hospital,China(QNC19051)+2 种基金National Key Basic Research Program of China,China(2014CB943001)China Postdoctoral Science Foundation,China(2017M613326)Key Research and Development Project of Hainan Province,China(ZDYF2017076).
文摘Background:Sudden sensorineural hearing loss(SSHL)refers to the sudden occurrence of unexplained sensorineural hearing loss.The present study showed that different systemic diseases had different influence on the occurrence and hearing outcome of SSHL.Thyroid hormone is one of the important factors for the development of fetal ear and auditory function.However,the distribution of thyroid dysfunction in SSHL patients and the effect of thyroid dysfunction on the occurrence and hearing outcome of SSHL has not been studied.Methods:In this study,a retrospective analysis had been done in 676 patients with SSHL.We had described the distribution of thyroid function in patients with SSHL in detail,and by the statistical method,analyzed the relationship between the hearing outcome and thyroid dysfunction,respectively.Results:In all patients,24.41%(165/676)had abnormal thyroid function testing results.The onset age of SSHL in FT3 abnormal group(including low and high group)was younger than that in normal FT3 group.Recovery group had more patients with lower-than-normal T3 level as compared to non-recovery patients.Significant associations between T3 levels and hearing outcome were observed in the subgroup with longer time elapse between symptom onset and treatment(≥14 d).Conclusion:The incidence of thyroid dysfunction in SSHL is significantly higher than in the general population.There was obvious relationship between T3 and FT3 item of thyroid dysfunction and the onset time and hearing outcome of SSHL,which indicated that T3 or FT3 indicator may be one of the affecting factors for the SSHL.Early screening and diagnosis of thyroid dysfunction,especial T3 level,may help to evaluate the prognosis in SSHL patients.
