Spherocytosis, Type 5

A number sign (#) is used with this entry because hereditary spherocytosis type 5 is caused by mutation in the gene encoding protein 4.2 (EPB42; 177070) on chromosome 15q15.

For a general phenotypic description and a discussion of genetic heterogeneity of hereditary spherocytosis, see SPH1 (182900).

Clinical Features

Hereditary spherocytosis type 5, which has been observed predominantly in Japanese individuals, is an autosomal recessive disorder that results in a hemolytic anemia associated with abnormally shaped, osmotically fragile red blood cells (Bouhassira et al., 1992).

Hayashi et al. (1974) described 4 Japanese patients, 3 of whom were sibs, with hereditary spherocytosis and deficiency of protein 4.2.

Nozawa et al. (1974) reported a severe case of hereditary spherocytosis in a 6-year-old Japanese girl with protein 4.2 deficiency who showed improvement with splenectomy.

Rybicki et al. (1988) noted that protein 4.2 is partially or completely absent in Japanese patients with recessive spherocytosis. In 1 Japanese patient with protein 4.2 deficiency, Rybicki et al. (1988) found that ankyrin was much less firmly associated with the membrane skeleton than normal.

Ideguchi et al. (1990) found deficiency of band 4.2 protein as the cause of an autosomal recessive form of hereditary spherocytosis in a Japanese brother and sister.

Ghanem et al. (1990) described complete absence of protein 4.2 in 2 Tunisian sibs. The proposita presented with hemolytic anemia cured by splenectomy. Her red cells had normal morphology. Her sister also had hemolytic anemia. The parents were first cousins and were clinically normal, with morphologically normal red cells which had a normal content of protein 4.2. This may indicate that the primary defect does not reside in the 4.2 gene, but rather in another element of the red cell membrane skeleton essential for stabilization of protein 4.2. This appears to be the first instance of absent protein 4.2 outside of Japan.

Molecular Genetics

In 4 unrelated Japanese patients with hereditary spherocytosis, Bouhassira et al. (1991, 1992) identified homozygosity for a mutation in the EPB42 gene (177070.0001).

In a Portuguese woman with recessively transmitted hemolytic anemia, Hayette et al. (1995) identified a mutation in the EPB42 gene (177070.0002).

In Tunisian sibs with autosomal recessive hemolytic anemia reported by Ghanem et al. (1990), Hayette et al. (1995) identified homozygosity for a mutation in the EPB42 gene (177070.0003).