ClinVar

Van Maldergem Syndrome 2

In a patient (F2) with Van Maldergem syndrome-2 (VMLDS2; 615546), Cappello et al. (2013) identified compound heterozygous mutations in the FAT4 gene: a c.7123G-A transition in exon 7, resulting in a glu2375-to-lys (E2375K) substitution in the CR23 domain, and a c.9481G-T transversion in exon 9, resulting in a glu3161-to-ter (E3161X; 612411.0004) substitution in the CR30 domain. The mutations segregated with the disorder in this family, and E2375K was not present in the dbSNP or 1000 Genomes Project databases. Glu2375 chelates calcium within the cadherin interdomain linker region. The patient had previously been reported as patient 6 by Mansour et al. (2012).

Hennekam Lymphangiectasia-Lymphedema Syndrome 2

In 3 affected members of a consanguineous Dutch family with Hennekam lymphangiectasia-lymphedema syndrome-2 (HKLLS2; 616006), originally reported by Hennekam et al. (1989), Alders et al. (2014) identified a homozygous c.7123G-A transition in the FAT4 gene, resulting in an E2375K substitution at a highly conserved residue. The mutation, which was found using a combination of homozygosity mapping and whole-exome sequencing, segregated with the disorder in the family and was not present in the dbSNP, 1000 Genomes Project, or Exome Sequencing Project databases, or in 20 control exomes. Functional studies of the variant were not performed. (In the article by Alders et al. (2014), this mutation was cited as E2375K in some places and as E2375R in others; Hennekam (2014) confirmed that E2375K is correct.)