Family pedigrees and corresponding <i>KISS1R</i> mutations.

<p><b>Panel A.</b> Pedigree of the family with homozygous <i>KISS1R</i> c.937T>C mutation. The proband, subject II-8 (arrow), and his two affected sisters, subjects II-1 and II-3, were homozygous for the c.937T>C mutation. The unaffected mother (I-1) and father (I-2) were heterozygous for the same mutation. Two unaffected sisters, II-6 and II-7, carried two wild-type alleles. This missense mutation (p.Tyr313His, (H)) is located in the seventh transmembrane segment. Squares represent males and circles females. Solid symbols indicate affected subjects and half-shaded symbols unaffected heterozygous. <b>Panel B.</b> Pedigree of the family with compound heterozygous <i>KISS1R</i> mutations c.305T>C and c.1195T>A. The proband, subject II-1 (arrow), was a compound heterozygote for the <i>KISS1R</i> mutations c.305T>C and c.1195T>A. The unaffected mother (I-1) was heterozygous for the c.305T>C mutation. The unaffected father was deceased and therefore unavailable for genetic analysis. The c.305T>C substitution produces a missense mutation (p.Leu102Pro, (P)) in the second transmembrane segment of KISS1R. The c.1195T>A substitution abolishes the natural stop codon (p.Stop399Arg, (R)). Small black circles indicate miscarriages. <b>Panel C.</b> Results of automatic DNA <i>KISS1R</i> sequencing encompassing the c.937T>C homozygous mutation in the propositus, compared to an unaffected control (lower panel). Inframe amino acids are indicated above each sequence. <b>Panel D.</b> Schematic representation of <i>KISS1R</i> and location of the mutations. <b>Panel E.</b> Results of automatic DNA <i>KISS1R</i> sequencing encompassing the c.305T>C and c.1195T>A compound heterozygous mutations in the propositus. Inframe amino acids are indicated above each sequence.