Study of the family of a patient with male-limited precocious puberty (MPP) due to T1193C transition in exon 11 of LH receptor gene

Abstract

Molecular diagnostics of the LHR gene was conducted in a 5-year-old boy with clinical symptoms and hormonal profile typical of precocious puberty. His parents and 4 sisters were also diagnosed. Single-strand conformation polymorphism analysis under temperature gradient conditions (Multitemperature SSCP) of 3 overlapping fragments of exon 11 of LHR gene revealed a mutation in the fragment spanning nucleotides 1072 to 1804. This mutation was found in the patient, in his mother and in his 4 sisters, and was confirmed by digestion with the use of restriction enzyme Bbr Cl. Direct sequencing revealed a heterozygous T1193C transition in the DNA fragment of the patient and in one of the alleles of his mother's and sister's DNA. This mutation causes Met398Thr substitution in the second transmembrane helix and results in a constitutive activation of LH receptor. This is the second identical mutation detected in Poland and one of the 7 identified so far in the world population.