# 612690

SPHEROCYTOSIS, TYPE 5; SPH5


Alternative titles; symbols

SPHEROCYTOSIS, HEREDITARY, 5; HS5


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
15q15.2 Spherocytosis, type 5 612690 3 EPB42 177070

TEXT

A number sign (#) is used with this entry because of evidence that hereditary spherocytosis type 5 is caused by homozygous 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 (SPH5), 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.


Inheritance

The transmission pattern of SPH5 in the patients reported by Bouhassira et al. (1991, 1992) was consistent with autosomal recessive inheritance.


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).


REFERENCES

  1. Bouhassira, E. E., Schwartz, R. S., Yawata, Y., Ata, K., Kanzaki, A., Qui, J. J.-H., Nagel, R. L., Rybicki, A. C. An alanine-to-threonine substitution in protein 4.2 cDNA is associated with a Japanese form of hereditary hemolytic anemia (protein 4.2-Nippon). Blood 79: 1846-1854, 1992. [PubMed: 1558976, related citations]

  2. Bouhassira, E. E., Schwartz, R. S., Yawata, Y., Ata, K., Nagel, R. L., Rybicki, A. C. An alanine to threonine substitution in protein 4.2 cDNA is associated with a Japanese form of hereditary hemolytic anemia. (Abstract) Clin. Res. 39: 313A, 1991.

  3. Ghanem, A., Pothier, B., Marechal, J., Ducluzeau, M. T., Morle, L., Alloisio, N., Feo, C., Ben Abdeladhim, A., Fattoum, S., Delaunay, J. A haemolytic syndrome associated with the complete absence of red cell membrane protein 4.2 in two Tunisian siblings. Brit. J. Haemat. 75: 414-420, 1990. [PubMed: 2386772, related citations] [Full Text]

  4. Hayashi, S., Koomoto, R., Yano, A., Ishigami, S., Tsujino, G., Saeki, S., Tanaka, T. Abnormality in a specific protein of the erythrocyte membrane in hereditary spherocytosis. Biochem. Biophys. Res. Commun. 57: 1038-1044, 1974. [PubMed: 4830746, related citations] [Full Text]

  5. Hayette, S., Dhermy, D., dos Santos, M.-E., Bozon, M., Drenckhahn, D., Alloisio, N., Texier, P., Delaunay, J., Morle, L. A deletional frameshift mutation in protein 4.2 gene (allele 4.2 Lisboa) associated with hereditary hemolytic anemia. Blood 85: 250-256, 1995. [PubMed: 7803799, related citations]

  6. Hayette, S., Morle, L., Bozon, M., Ghanem, A., Risinger, M., Korsgren, C., Tanner, M. J. A., Fattoum, S., Cohen, C. M., Delaunay, J. A point mutation in the protein 4.2 gene (allele 4.2 Tozeur) associated with hereditary haemolytic anaemia. Brit. J. Haemat. 89: 762-770, 1995. [PubMed: 7772513, related citations] [Full Text]

  7. Ideguchi, H., Nishimura, J., Nawata, H., Hamasaki, N. A genetic defect of erythrocyte band 4.2 protein associated with hereditary spherocytosis. Brit. J. Haemat. 74: 347-353, 1990. [PubMed: 2139792, related citations] [Full Text]

  8. Nozawa, Y., Noguchi, T., Iida, H., Fukushima, H., Sekiya, T., Ito, Y. Erythrocyte membranes in hereditary spherocytosis: alterations in surface ultrastructure and membrane proteins as inferred by scanning electron microscopy and SDS gel electrophoresis. Clin. Chim. Acta 55: 81-85, 1974. [PubMed: 4413274, related citations] [Full Text]

  9. Rybicki, A. C., Heath, R., Wolf, J. L., Lubin, B., Schwartz, R. S. Deficiency of protein 4.2 in erythrocytes from a patient with a Coombs negative hemolytic anemia: evidence for a role of protein 4.2 in stabilizing ankyrin on the membrane. J. Clin. Invest. 81: 893-901, 1988. [PubMed: 2963832, related citations] [Full Text]


Creation Date:
Carol A. Bocchini : 3/24/2009
carol : 12/12/2023
carol : 03/24/2022
carol : 03/25/2009
carol : 3/24/2009
carol : 3/24/2009

# 612690

SPHEROCYTOSIS, TYPE 5; SPH5


Alternative titles; symbols

SPHEROCYTOSIS, HEREDITARY, 5; HS5


ORPHA: 822;   DO: 0110920;  


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
15q15.2 Spherocytosis, type 5 612690 3 EPB42 177070

TEXT

A number sign (#) is used with this entry because of evidence that hereditary spherocytosis type 5 is caused by homozygous 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 (SPH5), 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.


Inheritance

The transmission pattern of SPH5 in the patients reported by Bouhassira et al. (1991, 1992) was consistent with autosomal recessive inheritance.


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).


REFERENCES

  1. Bouhassira, E. E., Schwartz, R. S., Yawata, Y., Ata, K., Kanzaki, A., Qui, J. J.-H., Nagel, R. L., Rybicki, A. C. An alanine-to-threonine substitution in protein 4.2 cDNA is associated with a Japanese form of hereditary hemolytic anemia (protein 4.2-Nippon). Blood 79: 1846-1854, 1992. [PubMed: 1558976]

  2. Bouhassira, E. E., Schwartz, R. S., Yawata, Y., Ata, K., Nagel, R. L., Rybicki, A. C. An alanine to threonine substitution in protein 4.2 cDNA is associated with a Japanese form of hereditary hemolytic anemia. (Abstract) Clin. Res. 39: 313A, 1991.

  3. Ghanem, A., Pothier, B., Marechal, J., Ducluzeau, M. T., Morle, L., Alloisio, N., Feo, C., Ben Abdeladhim, A., Fattoum, S., Delaunay, J. A haemolytic syndrome associated with the complete absence of red cell membrane protein 4.2 in two Tunisian siblings. Brit. J. Haemat. 75: 414-420, 1990. [PubMed: 2386772] [Full Text: https://doi.org/10.1111/j.1365-2141.1990.tb04357.x]

  4. Hayashi, S., Koomoto, R., Yano, A., Ishigami, S., Tsujino, G., Saeki, S., Tanaka, T. Abnormality in a specific protein of the erythrocyte membrane in hereditary spherocytosis. Biochem. Biophys. Res. Commun. 57: 1038-1044, 1974. [PubMed: 4830746] [Full Text: https://doi.org/10.1016/0006-291x(74)90801-8]

  5. Hayette, S., Dhermy, D., dos Santos, M.-E., Bozon, M., Drenckhahn, D., Alloisio, N., Texier, P., Delaunay, J., Morle, L. A deletional frameshift mutation in protein 4.2 gene (allele 4.2 Lisboa) associated with hereditary hemolytic anemia. Blood 85: 250-256, 1995. [PubMed: 7803799]

  6. Hayette, S., Morle, L., Bozon, M., Ghanem, A., Risinger, M., Korsgren, C., Tanner, M. J. A., Fattoum, S., Cohen, C. M., Delaunay, J. A point mutation in the protein 4.2 gene (allele 4.2 Tozeur) associated with hereditary haemolytic anaemia. Brit. J. Haemat. 89: 762-770, 1995. [PubMed: 7772513] [Full Text: https://doi.org/10.1111/j.1365-2141.1995.tb08413.x]

  7. Ideguchi, H., Nishimura, J., Nawata, H., Hamasaki, N. A genetic defect of erythrocyte band 4.2 protein associated with hereditary spherocytosis. Brit. J. Haemat. 74: 347-353, 1990. [PubMed: 2139792] [Full Text: https://doi.org/10.1111/j.1365-2141.1990.tb02594.x]

  8. Nozawa, Y., Noguchi, T., Iida, H., Fukushima, H., Sekiya, T., Ito, Y. Erythrocyte membranes in hereditary spherocytosis: alterations in surface ultrastructure and membrane proteins as inferred by scanning electron microscopy and SDS gel electrophoresis. Clin. Chim. Acta 55: 81-85, 1974. [PubMed: 4413274] [Full Text: https://doi.org/10.1016/0009-8981(74)90336-2]

  9. Rybicki, A. C., Heath, R., Wolf, J. L., Lubin, B., Schwartz, R. S. Deficiency of protein 4.2 in erythrocytes from a patient with a Coombs negative hemolytic anemia: evidence for a role of protein 4.2 in stabilizing ankyrin on the membrane. J. Clin. Invest. 81: 893-901, 1988. [PubMed: 2963832] [Full Text: https://doi.org/10.1172/JCI113400]


Creation Date:
Carol A. Bocchini : 3/24/2009

Edit History:
carol : 12/12/2023
carol : 03/24/2022
carol : 03/25/2009
carol : 3/24/2009
carol : 3/24/2009