Alternative titles; symbols
SNOMEDCT: 111390002, 237870002; ORPHA: 353220; DO: 0080930;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 5p13.1 | Amyloidosis, primary localized cutaneous, 1 | 105250 | Autosomal dominant | 3 | OSMR | 601743 |
A number sign (#) is used with this entry because of evidence that familial primary localized cutaneous amyloidosis-1 is caused by heterozygous mutation in the gene encoding oncostatin M receptor-beta (OSMR; 601743) on chromosome 5p13.
Primary localized cutaneous amyloidosis is characterized clinically by pruritus and skin scratching and histologically by the finding of deposits of amyloid staining on keratinous debris in the papillary dermis (summary by Tanaka et al., 2009).
Genetic Heterogeneity of Primary Localized Cutaneous Amyloidosis
Primary localized cutaneous amyloidosis-2 (PLCA2; 613955) is caused by heterozygous mutation in the IL31RA gene (609510) on chromosome 5q11. Primary localized cutaneous amyloidosis-3 (PLCA3; 617920) is caused by mutation in the GPNMB gene (604368) on chromosome 7p15.
Sagher and Shanon (1963) found 3 cases of primary cutaneous amyloidosis in 3 generations of a Russian-Jewish family. Tay (1971) reported affected mother and daughter.
Rajagopalan and Tay (1972) reported 19 persons in 4 successive generations of a Chinese family in Malaysia. Onset was around the age of puberty. The extent of cutaneous involvement increased with age but no systemic involvement occurred. There are at least 2 reports of affected sibs.
Eng et al. (1976) described brother and sister with amyloid of the skin of a type possibly different from that in the other reports.
Newton et al. (1985) described a British family. The subtlety of physical signs contrasted with the severity of the associated pruritus. Transepidermal elimination of amyloid was a characteristic histologic feature. When scratching, patients were able to remove the 'core' of the papules with consequent reduction in pruritus. Four generations and by inference a fifth were affected.
Primary Cutaneous Amyloidosis Associated with Multiple Endocrine Neoplasia Type IIA
PLCA has been described in association with other disorders, including multiple endocrine neoplasia type IIA (MEN2A; 171400). The cutaneous lichen amyloidosis that occurs in MEN2A is associated with pruritus and occurs particularly in the interscapular region. It is thought to be a form of 'friction amyloidosis' and to be related to notalgia paresthetica, a neuropathy of the posterior dorsal nerve rami. A cys634-to-tyr missense mutation in the RET gene (164761.0004) was identified in affected members of one family with MEN2A and cutaneous lichen amyloidosis (Ceccherini et al., 1994). Seri et al. (1997) reported a family in which multiple members with MEN2A and cutaneous lichen amyloidosis had a cys634-to-gly mutation in the RET gene (164761.0003). Tanaka et al. (2009) stated that, despite these reports, there is no evidence to suggest that PLCA in MEN2A results directly from mutations in the RET gene; rather, there is indirect evidence that the amyloid deposition is a secondary phenomenon.
Most cases of primary localized cutaneous amyloidosis are sporadic. PLCA1 is inherited in an autosomal dominant manner (Arita et al., 2008).
Familial primary cutaneous amyloidosis occurs more frequently in certain populations, i.e,, in China, Southeast Asia, and South America (Tanaka et al., 2009).
Genomewide scans for familial PLCA in Taiwan (Lin et al., 2005; Lee et al., 2006) achieved the most significant lod scores for the disease locus on chromosome 5p13.1-q11.2.
Arita et al. (2008) mapped the disorder in a large Brazilian family to 5p13.1-q11.2.
Exclusion Studies
Since some patients with multiple endocrine neoplasia type 2A have the clinical picture of primary cutaneous amyloidosis, Lee et al. (1996) carried out linkage analysis in 7 families with cutaneous amyloidosis using 4 dinucleotide repeat markers from the RET region. Negative lod scores and all recombination frequencies were obtained. They thus concluded that there is no evidence for linkage between Chinese families with primary cutaneous amyloidosis of the pericentromeric region of chromosome 10.
By candidate gene analysis of genes in the PLCA critical mapping region of chromosome 5, Arita et al. (2008) identified heterozygous missense mutations in the OSMR gene (601743.0001-601743.0002) in affected individuals of a large Brazilian family and in 2 other families, one from the United Kingdom and one from South Africa.
By whole-exome sequencing of the OSMR gene in Taiwanese patients with PLCA mapping to chromosome 5, Lin et al. (2010) identified 3 novel heterozygous mutations (601743.0003-601743.0005).
Exclusion Studies
Hofstra et al. (1996) screened 3 pedigrees with familial cutaneous lichen amyloidosis for RET mutations and found none in the RET coding and flanking intronic sequences. They interpreted this as indicating that skin amyloidosis found in some MEN2A families and familial cutaneous lichen amyloidosis are different conditions.
Arita, K., South, A. P., Hans-Filho, G., Sakuma, T. H., Lai-Cheong, J., Clements, S., Odashiro, M., Odashiro, D. N., Hans-Neto, G., Hans, N. R., Holder, M. V., Bhogal, B. S., Hartshorne, S. T., Akiyama, M., Shimizu, H., McGrath, J. A. Oncostatin M receptor-beta mutations underlie familial primary localized cutaneous amyloidosis. Am. J. Hum. Genet. 82: 73-80, 2008. [PubMed: 18179886] [Full Text: https://doi.org/10.1016/j.ajhg.2007.09.002]
Ceccherini, I., Romei, C., Barone, V., Pacini, F., Martino, E., Loviselli, A., Pinchera, A., Romeo, G. Identification of the cys634-to-tyr mutation of the RET proto-oncogene in a pedigree with multiple endocrine neoplasia type 2A and localized cutaneous lichen amyloidosis. J. Endocr. Invest. 17: 201-204, 1994. [PubMed: 7914213] [Full Text: https://doi.org/10.1007/BF03347719]
De Pietro, W. P. Primary familial cutaneous amyloidosis: a study of HLA antigens in a Puerto Rican family. Arch. Derm. 117: 639-642, 1981. [PubMed: 6945068] [Full Text: https://doi.org/10.1001/archderm.117.10.639]
Eng, A. M., Cogan, L., Gunnar, R. M., Blekys, I. Familial generalized dyschromic amyloidosis cutis. J. Cutan. Path. 3: 102-108, 1976. [PubMed: 993396] [Full Text: https://doi.org/10.1111/j.1600-0560.1976.tb00853.x]
Hofstra, R. M. W., Sijmons, R. H., Stelwagen, T., Stulp, R. P., Kousseff, B. G., Lips, C. J. M., Steijlen, P. M., Van Voorst Vader, P. C., Buys, C. H. C. M. RET mutation screening in familial cutaneous lichen amyloidosis and in skin amyloidosis associated with multiple endocrine neoplasia. J. Invest. Derm. 107: 215-218, 1996. [PubMed: 8757765] [Full Text: https://doi.org/10.1111/1523-1747.ep12329651]
Lee, D.-D., Huang, J.-Y., Wong, C.-K., Gagel, R. F., Tsai, S.-F. Genetic heterogeneity of familial primary cutaneous amyloidosis: lack of evidence for linkage with the chromosome 10 pericentromeric region in Chinese families. J. Invest. Derm. 107: 30-33, 1996. [PubMed: 8752835] [Full Text: https://doi.org/10.1111/1523-1747.ep12297840]
Lee, D.-D., Lin, M.-W., Chen, I.-C., Huang, C.-Y., Liu, M.-T., Wang, C.-R., Chang, Y.-T., Liu, H.-N., Liu, T.-T., Wong, C.-K., Tsai, S.-F. Genome-wide scan identifies a susceptibility locus for familial primary cutaneous amyloidosis on chromosome 5p13.1-q11.2. Brit. J. Derm. 155: 1201-1208, 2006. [PubMed: 17107390] [Full Text: https://doi.org/10.1111/j.1365-2133.2006.07524.x]
Lin, M.-W., Lee, D.-D., Lin, C.-H., Huang, C.-Y., Wong, C.-K., Chang, Y.-T., Liu, H.-N., Hsaio, K.-J., Tsai, S.-F. Suggestive linkage of primary cutaneous amyloidosis to a locus on chromosome 1q23. Brit. J. Derm. 152: 29-36, 2005. [PubMed: 15656797] [Full Text: https://doi.org/10.1111/j.1365-2133.2004.06254.x]
Lin, M.-W., Lee, D.-D., Liu, T.-T., Lin, Y.-F., Chen, S.-Y., Huang, C.-C., Weng, H.-Y., Liu, Y.-F., Tanaka, A., Arita, K., Lai-Cheong, J., Palisson, F., Chang, Y.-T., Wong, C.-K., Matsuura, I., McGrath, J. A., Tsai, S.-F. Novel IL31RA gene mutation and ancestral OSMR mutant allele in familial primary cutaneous amyloidosis. Europ. J. Hum. Genet. 18: 26-32, 2010. [PubMed: 19690585] [Full Text: https://doi.org/10.1038/ejhg.2009.135]
Newton, J. A., Jagjivan, A., Bhogal, B., McKee, P. H., McGibbon, D. H. Familial primary cutaneous amyloidosis. Brit. J. Derm. 112: 201-208, 1985. [PubMed: 3970841] [Full Text: https://doi.org/10.1111/j.1365-2133.1985.tb00084.x]
Ozaki, M. Familial lichen amyloidosis. Int. J. Derm. 23: 190-193, 1984. [PubMed: 6724776] [Full Text: https://doi.org/10.1111/j.1365-4362.1984.tb04509.x]
Rajagopalan, K. V., Tay, C. H. Familial lichen amyloidosis: report of 19 cases in 4 generations of a Chinese family in Malaysia. Brit. J. Derm. 87: 123-129, 1972. [PubMed: 5057380] [Full Text: https://doi.org/10.1111/j.1365-2133.1972.tb16186.x]
Sagher, F., Shanon, J. Amyloidosis cutis: familial occurrence in three generations. Arch. Derm. 87: 171-175, 1963. [PubMed: 13976058] [Full Text: https://doi.org/10.1001/archderm.1963.01590140033005]
Seri, M., Celli, I., Betsos, N., Claudiani, F., Camera, G., Romeo, G. A cys634gly substitution of the RET proto-oncogene in a family with recurrence of multiple endocrine neoplasia type 2A and cutaneous lichen amyloidosis. Clin. Genet. 51: 86-90, 1997. [PubMed: 9111993] [Full Text: https://doi.org/10.1111/j.1399-0004.1997.tb02425.x]
Shanon, J., Sagher, F. Interscapular cutaneous amyloidosis. Arch. Derm. 102: 195-198, 1970. [PubMed: 5430314]
Tanaka, A., Arita, K., Lai-Cheong, J. E., Palisson, F., Hide, M., McGrath, J. A. New insight into mechanisms of pruritus from molecular studies on familial primary localized cutaneous amyloidosis. Brit. J. Derm. 161: 1217-1224, 2009. [PubMed: 19663869] [Full Text: https://doi.org/10.1111/j.1365-2133.2009.09311.x]
Tay, C. H. Genodermatosis in Singapore. Asian J. Med. 7: 413 only, 1971.