PDF(Pubmed)
Abstract：
Deleterious variants of DYNC2H1 gene are associated with a wide spectrum of skeletal ciliopathies (SC). We used targeted parallel sequencing to analyze 25 molecularly unsolved families with different SCs. Deleterious DYNC2H1 variants were found in six sporadic patients and two monozygotic (MZ) twins. Clinical diagnoses included short rib-polydactyly type 3 in two cases, and asphyxiating thoracic dystrophy (ATD) in one case. Remarkably, clinical diagnosis fitted with EvC, mixed ATD/EvC and short rib-polydactyly/EvC phenotypes in three sporadic patients and the MZ twins. EvC/EvC-like features always occurred in compound heterozygotes sharing a previously unreported splice site change (c.6140-5A>G) or compound heterozygotes for two missense variants. These results expand the DYNC2H1 mutational repertoire and its clinical spectrum, suggesting that EvC may be occasionally caused by DYNC2H1 variants presumably acting as hypomorphic alleles.
摘要：
DYNC2H1基因的有害变体与广泛的骨骼纤毛病（SC）有关。我们使用靶向平行测序来分析具有不同SC的25个分子未溶解家族。在六名散发性患者和两名单卵（MZ）双胞胎中发现了有害的DYNC2H1变体。临床诊断包括短肋骨-多指3型2例，1例窒息性胸廓营养不良(ATD)。值得注意的是,符合EvC的临床诊断，3例散发性患者和MZ双胞胎的混合ATD/EvC和短肋骨多指/EvC表型。EvC/EvC样特征总是出现在具有先前未报道的剪接位点变化（c.6140-5A>G）的复合杂合子或两个错义变体的复合杂合子中。这些结果扩展了DYNC2H1突变库及其临床谱，这表明EvC可能偶尔是由DYNC2H1变体引起的，大概是低态等位基因。
