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Suggestive linkage of familial primary cutaneous amyloidosis to a locus on chromosome 1q23.
Br J Dermatol. 2005 Jan; 152(1):29-36.BJ

Abstract

BACKGROUND

There is a high incidence of primary cutaneous amyloidosis (PCA) in South America, South-east Asia and Taiwan. To date, the aetiology of PCA remains unknown, but it is believed to be multifactorial. Although most cases are sporadic, some patients have a family history. Familial aggregation and different susceptibility to PCA among ethnic groups suggest that genetic factors may play an important role in its pathogenesis. However, no genetic loci for familial PCA (FPCA) have been identified so far.

OBJECTIVES

In order to identify the susceptibility gene of FPCA, we took a candidate gene approach and performed linkage analysis on chromosome 1q21.3-24.2, including the 1q23.2 region where the gene encoding serum amyloid P component (APCS) is located.

PATIENTS AND METHODS

Nine FPCA families including 29 individuals affected with PCA were recruited for this linkage study. Initially, 11 highly polymorphic microsatellite markers spanning the region from 1q21.3 to 1q24.2 were genotyped and revealed a suggestive linkage region. This region was further fine-mapped with seven additional markers. We also re-sequenced the 2.5-kb genomic region of the APCS gene in 29 affected and 42 control individuals. Two-point and multipoint linkage analyses were performed using the LINKAGE program. Nonparametric linkage (NPL) analysis and reconstruction of haplotypes were performed with the GENEHUNTER program.

RESULTS

Both two-point and multipoint linkage analysis for all 11 markers generated negative or small positive total lod scores for all nine families. However, when we considered only three families, a maximum two-point total lod score of 2.09 was obtained for the marker D1S2844 at theta = 0.01. A plateau of multipoint total lod score between D1S2768 and D1S2878 with a maximum of 2.48 at the marker D1S2844 was observed. A maximum NPL score of 3.11 (P = 0.008) was also obtained for the marker D1S2878. However, re-sequencing of the APCS gene identified no functional mutation.

CONCLUSIONS

Both parametric and nonparametric linkage evidence suggested that a possible susceptibility locus for a subset of FPCA might exist on chromosome 1q23. This is the first report demonstrating suggestive evidence of linkage of FPCA to a locus in this candidate region. No functional sequence variations of the APCS gene were found to be associated with this disease among the study families. Our data imply the existence of at least one additional locus responsible for FPCA in these families, confirming genetic heterogeneity of this skin disorder.

Authors+Show Affiliations

Department of Family Medicine, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15656797

Citation

Lin, M-W, et al. "Suggestive Linkage of Familial Primary Cutaneous Amyloidosis to a Locus On Chromosome 1q23." The British Journal of Dermatology, vol. 152, no. 1, 2005, pp. 29-36.
Lin MW, Lee DD, Lin CH, et al. Suggestive linkage of familial primary cutaneous amyloidosis to a locus on chromosome 1q23. Br J Dermatol. 2005;152(1):29-36.
Lin, M. W., Lee, D. D., Lin, C. H., Huang, C. Y., Wong, C. K., Chang, Y. T., Liu, H. N., Hsiao, K. J., & Tsai, S. F. (2005). Suggestive linkage of familial primary cutaneous amyloidosis to a locus on chromosome 1q23. The British Journal of Dermatology, 152(1), 29-36.
Lin MW, et al. Suggestive Linkage of Familial Primary Cutaneous Amyloidosis to a Locus On Chromosome 1q23. Br J Dermatol. 2005;152(1):29-36. PubMed PMID: 15656797.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Suggestive linkage of familial primary cutaneous amyloidosis to a locus on chromosome 1q23. AU - Lin,M-W, AU - Lee,D-D, AU - Lin,C-H, AU - Huang,C-Y, AU - Wong,C-K, AU - Chang,Y-T, AU - Liu,H-N, AU - Hsiao,K-J, AU - Tsai,S-F, PY - 2005/1/20/pubmed PY - 2005/4/15/medline PY - 2005/1/20/entrez SP - 29 EP - 36 JF - The British journal of dermatology JO - Br. J. Dermatol. VL - 152 IS - 1 N2 - BACKGROUND: There is a high incidence of primary cutaneous amyloidosis (PCA) in South America, South-east Asia and Taiwan. To date, the aetiology of PCA remains unknown, but it is believed to be multifactorial. Although most cases are sporadic, some patients have a family history. Familial aggregation and different susceptibility to PCA among ethnic groups suggest that genetic factors may play an important role in its pathogenesis. However, no genetic loci for familial PCA (FPCA) have been identified so far. OBJECTIVES: In order to identify the susceptibility gene of FPCA, we took a candidate gene approach and performed linkage analysis on chromosome 1q21.3-24.2, including the 1q23.2 region where the gene encoding serum amyloid P component (APCS) is located. PATIENTS AND METHODS: Nine FPCA families including 29 individuals affected with PCA were recruited for this linkage study. Initially, 11 highly polymorphic microsatellite markers spanning the region from 1q21.3 to 1q24.2 were genotyped and revealed a suggestive linkage region. This region was further fine-mapped with seven additional markers. We also re-sequenced the 2.5-kb genomic region of the APCS gene in 29 affected and 42 control individuals. Two-point and multipoint linkage analyses were performed using the LINKAGE program. Nonparametric linkage (NPL) analysis and reconstruction of haplotypes were performed with the GENEHUNTER program. RESULTS: Both two-point and multipoint linkage analysis for all 11 markers generated negative or small positive total lod scores for all nine families. However, when we considered only three families, a maximum two-point total lod score of 2.09 was obtained for the marker D1S2844 at theta = 0.01. A plateau of multipoint total lod score between D1S2768 and D1S2878 with a maximum of 2.48 at the marker D1S2844 was observed. A maximum NPL score of 3.11 (P = 0.008) was also obtained for the marker D1S2878. However, re-sequencing of the APCS gene identified no functional mutation. CONCLUSIONS: Both parametric and nonparametric linkage evidence suggested that a possible susceptibility locus for a subset of FPCA might exist on chromosome 1q23. This is the first report demonstrating suggestive evidence of linkage of FPCA to a locus in this candidate region. No functional sequence variations of the APCS gene were found to be associated with this disease among the study families. Our data imply the existence of at least one additional locus responsible for FPCA in these families, confirming genetic heterogeneity of this skin disorder. SN - 0007-0963 UR - https://www.unboundmedicine.com/medline/citation/15656797/Suggestive_linkage_of_familial_primary_cutaneous_amyloidosis_to_a_locus_on_chromosome_1q23_ L2 - https://doi.org/10.1111/j.1365-2133.2004.06254.x DB - PRIME DP - Unbound Medicine ER -