The gene for juvenile hyaline fibromatosis maps to chromosome 4q21

Abstract

Juvenile hyaline fibromatosis (JHF) is an autosomal recessive condition characterized by multiple subcutaneous nodular tumors, gingival fibromatosis, flexion contractures of the joints, and an accumulation of hyaline in the dermis. We performed a genomewide linkage search in two families with JHF from the same region of the Indian state of Gujarat and identified a region of homozygosity on chromosome 4q21. Dense microsatellite analyses within this interval in five families with JHF who were from diverse origins demonstrate that all are compatible with linkage to chromosome 4q21 (multipoint LOD score 5.5). Meiotic recombinants place the gene for JHF within a 7-cM interval bounded by D4S2393 and D4S395.

Figure 1

Haplotypes for 13 markers from chromosome 4q21 in five families with JHF. Blackened symbols indicate individuals affected with JHF. In families A–D, boxes around marker alleles indicate the region of homozygosity. In family E, all vertical bars next to the alleles indicate the segregating haplotypes and show that the parental chromosome 4q21 haplotypes inherited by the affected individual (ID 26) are different from those of his unaffected siblings. Critical meiotic recombinants in ID 11, ID 22, and ID 23 refine the minimal interval encompassing the JHF-predisposition gene to the region between D4S2393 and D4S395.

Figure 2

Hands of ID 7, showing nodular lesions and subcutaneous swellings that are typical of JHF

Figure 3

Combined multipoint LOD score at chromosome 4q21 in five families with JHF