Jervell And Lange-Nielsen Syndrome 2

A number sign (#) is used with this entry because of evidence that Jervell and Lange-Nielsen syndrome-2 (JLNS2) is caused by homozygous or compound heterozygous mutation in the KCNE1 gene (176261) on chromosome 21q22.

Long QT syndrome-5 (LQT5; 613695) is caused by heterozygous mutation in the KCNE1 gene.

Description

The Jervell and Lange-Nielsen syndrome is an autosomal recessive syndrome of abnormal cardiac ventricular repolarization with prolonged QT interval and bilateral congenital deafness.

For a general description and a discussion of genetic heterogeneity of Jervell and Lange-Nielsen syndrome, see 220400.

Mapping

In a small consanguineous British family with JLNS, Tyson et al. (1997) excluded linkage to KCNQ1 (607542), and found that the affected children were homozygous by descent for markers on chromosome 21, in a region containing the KCNE1 gene (176261). Tyson et al. (1997) found that most of the families they studied showed linkage consistent with mutation at the KCNQ1 gene.

Molecular Genetics

In a small consanguineous British family in which the JLNS phenotype had been mapped to chromosome 21, Tyson et al. (1997) detected a homozygous mutation in the KCNE1 gene (176261.0001). The KCNE1 gene encodes a transmembrane protein that associates with KCNQ1 to form the delayed rectifier potassium channel.

Schulze-Bahr et al. (1997) found compound heterozygosity for mutations in the KCNE1 gene (176261.0002, 176261.0003) in affected members of a Lebanese family with JLNS.

Duggal et al. (1998) reported a family in which a young girl with JLNS was homozygous for a mutation in the KCNE1 gene (176261.0003), whereas her heterozygous first-degree relatives showed a milder phenotype with partial hearing loss and QT prolongation more in keeping with LQT1.