Analysis ofc-kitexon 11 and exon 17 of urticaria pigmentosa that occurred in monozygotic twin sisters

Abstract

Genomic DNA extracted from peripheral blood mononuclear cells of monozygotic twin patients with urticaria pigmentosa was investigated for mutations of proto-oncogene c-kit. Neither the patients nor their families had genomic mutations in exon 11 or exon 17 of c-kit. The patients did not have any systemic involvement or bone marrow abnormalities. There are indications that some genetic factors may participate in the pathogenesis of urticaria pigmentosa in monozygotic twins. In the present patients, factors other than genomic faults in exon 11 and exon 17 of c-kit may be responsible for the pathogenesis.

Mastocytosis: recent advances in defining the disease

“…Interestingly, the cutaneous lesions in twins are usually very similar, and the onset as well as the spread of lesions occurs almost synchronously, suggesting that at least in these patients, genetic factors play an important part for the development of the disease. 13,18 Age at onset 17 Recent data demonstrating that patients with a familial association, in contrast to patients with sporadic mastocytosis, seem to lack c-kit mutations; therefore, this indicates that familial mastocytosis is a subgroup of the disease, with a different pathogenesis and prognosis.…”

“…61 In line with these observations, autonomous, ligand-independent growth of cultured mast cells was observed in patients with rapidly progressive mastocytosis, 62 and mast cells cultured from CD341 peripheral blood mononuclear cells of patients with mastocytosis resulted in higher numbers of mast cells, compared with cultures of healthy controls. 8,13,18 Expression of mast cell growth factors and of c-kit 13,46 The observation that three of six children with sporadic and presumably transient urticaria pigmentosa were found to carry an inactivating, dominant c-kit mutation in codon 839, substituting lysine for glutamic acid, is at present difficult to interpret regarding its pathological relevance.…”

“…55 Familial mastocytosis must be viewed as a separate entity as well, as genomic or somatic c-kit mutations could not be found in three families with several members suffering from mastocytosis. 8,13,18 Expression of mast cell growth factors and of c-kit…”

A novel A97P amino acid substitution in alpha-galactosidase A leads to a classical Fabry disease with cardiac manifestations

“…PCR and direct sequencing was performed as described previously. 6 The G fi C transversion in codon 97 of exon 2 was found within the proband in the hemizygous state. In the mother of the proband the mutation was found to be heterozygous.…”

“…The primer pairs were chosen based on exon/intron boundaries (Table 1). PCR and direct sequencing was performed as described previously 6 …”