Tyson J, Tranebjaerg L, McEntagart M, Larsen L A, Christiansen M, Whiteford M L, Bathen J, Aslaksen B, Sørland S J, Lund O, Pembrey M E, Malcolm S, Bitner-Glindzicz M
Clinical and Molecular Genetics Unit, Institute of Child Health, London, UK.
Hum Genet. 2000 Nov;107(5):499-503. doi: 10.1007/s004390000402.
Jervell and Lange-Nielsen syndrome (JLNS) is an autosomal recessive syndrome characterised by profound congenital sensorineural deafness and prolongation of the QT interval on the electrocardiogram, representing abnormal ventricular repolarisation. In a study of ten British and Norwegian families with JLNS, we have identified all of the mutations in the KCNQ1 gene, including two that are novel. Of the nine mutations identified in this group of 10 families, five are nonsense or frameshift mutations. Truncation of the protein proximal to the recently identified C-terminal assembly domain is expected to preclude assembly of KCNQ1 monomers into tetramers and explains the recessive inheritance of JLNS. However, study of a frameshift mutation, with a dominant effect phenotypically, suggests the presence of another assembly domain nearer to the N-terminus.
杰韦尔和朗格 - 尼尔森综合征（JLNS）是一种常染色体隐性综合征，其特征为严重的先天性感音神经性耳聋以及心电图上QT间期延长，这代表心室复极化异常。在一项针对十个患有JLNS的英国家庭和挪威家庭的研究中，我们已确定了KCNQ1基因中的所有突变，其中包括两个新发现的突变。在这10个家庭中鉴定出的9个突变中，有5个是无义或移码突变。预计在最近确定的C端组装结构域近端的蛋白质截短会阻止KCNQ1单体组装成四聚体，并解释了JLNS的隐性遗传。然而，对一个具有显性表型效应的移码突变的研究表明，在更靠近N端的位置存在另一个组装结构域。
