Ws. Wassif et al., FAMILIAL ISOLATED HYPERPARATHYROIDISM - A DISTINCT GENETIC ENTITY WITH AN INCREASED RISK OF PARATHYROID CANCER, The Journal of clinical endocrinology and metabolism, 77(6), 1993, pp. 1485-1489
Familial isolated hyperparathyroidism (FIHP) is a rare heritable disor
der characterized by hypercalcemia, inappropriately high PTH levels, a
nd isolated parathyroid tumors with no evidence of hyperfunction of an
y other endocrine tissues. To establish whether FIHP exists as a disti
nct disease entity or represents a variant of any of the known multipl
e endocrine neoplasia (MEN) syndromes, we tested 19 members of a large
, well characterized family with FIHP in which the disease is transmit
ted through 4 generations in an autosomal dominant fashion. Fourteen D
NA markers at 10 polymorphic loci closely linked to the MEN1 locus on
the long arm of chromosome 11 and 5 markers close to the MEN2A gene on
chromosome 10 were tested using Southern blot analysis and polymerase
chain reaction-based techniques. Additionally, two polymorphic marker
s (Mir1 and Mir2) within the prepro-PTH gene on the short arm of chrom
osome 11 were analyzed using denaturant gradient gel electrophoresis.
Linkage was clearly excluded between FIHP and the MEN1 and MEN2A loci
as well as to the PTH gene. Comparison of constitutional and tumor gen
otypes showed that constitutional heterozygosity was retained for mark
ers in the MEN1 and MEN2A regions as well as to the PTH gene in 4 tumo
rs from 3 affected members. In 1 individual, a parathyroid carcinoma w
as found after recurrence of hypercalcemia. We, therefore, propose tha
t autosomal dominant FIHP can occur as a genetically and clinically di
stinct entity with an increased risk of malignant transformation of pa
rathyroid tumors.