Hypomagnesemia 4, Renal

A number sign (#) is used with this entry because of evidence that renal hypomagnesemia-4 (HOMG4) is caused by homozygous mutation in the EGF gene (131530) on chromosome 4q25. One such family has been reported.

For a discussion of genetic heterogeneity of renal hypomagnesemia, see 602014.

Clinical Features

Geven et al. (1987) described 2 Dutch sisters, born of second-cousin parents, who had isolated hypomagnesemia due to renal loss. Serum calcium levels and urinary calcium excretion were normal. The sisters had seizures, mild to moderate psychomotor retardation, and brisk tendon reflexes.

Mapping

Groenestege et al. (2007) performed homozygosity mapping in the consanguineous Dutch family originally described by Geven et al. (1987) and obtained a lod score of 2.66 on chromosome 4 at an 18.4-cM interval between markers D4S2623 and D4S1575.

Molecular Genetics

Meij et al. (2003) analyzed the FXYD2 (601814), CLDN16 (603959), and SLC12A3 (600968) genes in 2 Dutch sisters with renal hypomagnesemia, originally reported by Geven et al. (1987), but found no mutations.

Following mapping studies in the Dutch family that showed linkage to chromosome 4, Groenestege et al. (2007) analyzed the candidate EGF gene (131530) and identified homozygosity for a mutation (P1070L; 131530.0001) in the 2 affected sisters. The unaffected parents and 2 unaffected sibs were heterozygous for the mutation, which was not found in 126 ethnically matched controls.