Segregation of Kallmann Syndrome and the <i>PROKR2</i> or <i>PROK2</i> Mutations in Affected Families

<p>Filled symbols denote clinically affected individuals with both hypogonadism and anosmia (or hyposmia). Half-filled symbols denote individuals with either anosmia only (right black part) or hypogonadism only (left black part). Genotypes, if available, are indicated below. The symbol + denotes normal allele, and fs stands for frameshift mutation. In several pedigrees the mutation is associated with varying phenotypes. Notably, in family A the disease apparently segregates according to a semi-dominant mode of transmission. The schematic representation of PROKR2 shows the locations of the nine missense mutations found in familial and non-familial KS cases, with respect to the putative N-terminal (N ter), C-terminal (C ter), extracellular loop (e1-e3), intracellular loop (i1-i3), and transmembrane (T1–T7) domains [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0020175#pgen-0020175-b013" target="_blank">13</a>] of this G protein-coupled receptor.</p

Sequences of the primers used to validate the mutations by Sanger sequencing.

<p>Sequences of the primers used to validate the mutations by Sanger sequencing.</p

Pedigrees of the four Tunisian families analyzed using the whole exome sequencing strategy.

<p>Pedigrees of the four Tunisian families analyzed using the whole exome sequencing strategy.</p

Evolution of the number of variants during whole exome.

<p>Evolution of the number of variants during whole exome.</p

Biallelic mutations identified in DFNB genes using a whole exome sequencing strategy.

<p>Biallelic mutations identified in DFNB genes using a whole exome sequencing strategy.</p