PDF(Pubmed)
Abstract：
UNASSIGNED: Ciliopathies with major skeletal involvement embrace a group of heterogeneous disorders caused by pathogenic variants in a group of diverse genes. A narrow thorax with shortening of long bones inspires a clinical entity underlined by dysfunction of primary cilia. Currently, more than 23 genes are listed in the OMIM database corresponding to this clinical entity: WDR19/34/35/60, IFT43/52/80/81/140/172, DYNC2LI1, TTC21B, DYNLT2B, EVC2, EVC, INTU, NEK1, CEP120, DYNC2H1, KIAA0586, SRTD1, KIAA0753, and SRTD12. Recently, individuals with biallelic loss-of-function variants in GRK2 are shown to demonstrate a phenotype compatible with Jeune syndrome. Experimental evidence has shown that impaired function of GRK2 compromises cilia-based signaling of Hedgehog pathway as well as Wnt signaling, while cilia morphology remains intact. Hence, GRK2 is now considered an essential protein in regulation of the skeletogenesis.
UNASSIGNED: We presented a female infant born to a consanguineous marriage who was found to have a biallelic p.R474* alteration in GRK2 in reanalysis of the whole-exome sequencing (WES) data. The patient was exhibiting major clinical features of Jeune syndrome, such as shortened long bones, ribs, and narrow thorax.
UNASSIGNED: Our reanalysis of WES data revealed a likely pathogenic biallelic variant in the GRK2 which is probably responsible for the Jeune syndrome phenotype in the patient. Hence, our report supports the recently discovered association of GRK2 loss-of-function variants with Jeune syndrome phenotype and emphasizes the significance of reanalysis of WES data, notably in patients with phenotypes suggestive of a such discernible Mendelian disorder.
UNASSIGNED: We presented a female infant born to a consanguineous marriage who was found to have a biallelic p.R474* alteration in GRK2 in reanalysis of the whole-exome sequencing (WES) data. The patient was exhibiting major clinical features of Jeune syndrome, such as shortened long bones, ribs, and narrow thorax.
UNASSIGNED: Our reanalysis of WES data revealed a likely pathogenic biallelic variant in the GRK2 which is probably responsible for the Jeune syndrome phenotype in the patient. Hence, our report supports the recently discovered association of GRK2 loss-of-function variants with Jeune syndrome phenotype and emphasizes the significance of reanalysis of WES data, notably in patients with phenotypes suggestive of a such discernible Mendelian disorder.
摘要：
■主要骨骼受累的纤毛病包括一组由一组不同基因的致病变异引起的异质性疾病。狭窄的胸部长骨缩短，激发了以初级纤毛功能障碍为重点的临床实体。目前,OMIM数据库中列出了与该临床实体相对应的超过23个基因：WDR19/34/35/60，IFT43/52/80/81/140/172，DYNC2LI1，TTC21B，DYNLT2B,EVC2、EVC、INTU,NEK1、CEP120、DYNC2H1、KIAA0586、SRTD1、KIAA0753和SRTD12。最近,GRK2中具有双等位基因功能丧失变异体的个体显示出与Jeune综合征相容的表型.实验证据表明，GRK2的功能受损会损害Hedgehog通路的纤毛信号以及Wnt信号，而纤毛形态保持完整。因此，GRK2现在被认为是调节骨骼形成的必需蛋白。
■我们介绍了一名近亲结婚的女性婴儿，在重新分析全外显子组测序（WES）数据时，发现GRK2有双等位基因p.R474*改变。患者表现出Jeune综合征的主要临床特征，如缩短的长骨，肋骨,胸部狭窄.
■我们对WES数据的重新分析揭示了GRK2中可能的致病性双等位基因变异，这可能是患者Jeune综合征表型的原因。因此，我们的报告支持最近发现的GRK2功能丧失变异与Jeune综合征表型的关联，并强调重新分析WES数据的重要性，尤其是在表型提示这种可辨别的孟德尔疾病的患者中。
■我们介绍了一名近亲结婚的女性婴儿，在重新分析全外显子组测序（WES）数据时，发现GRK2有双等位基因p.R474*改变。患者表现出Jeune综合征的主要临床特征，如缩短的长骨，肋骨,胸部狭窄.
■我们对WES数据的重新分析揭示了GRK2中可能的致病性双等位基因变异，这可能是患者Jeune综合征表型的原因。因此，我们的报告支持最近发现的GRK2功能丧失变异与Jeune综合征表型的关联，并强调重新分析WES数据的重要性，尤其是在表型提示这种可辨别的孟德尔疾病的患者中。
