Additional mutations in individuals with <i>LIPG</i> mutations and low HDLc.

<p>Additional mutations in individuals with <i>LIPG</i> mutations and low HDLc.</p

Representative segregation of mutations in families.

<p><b>A, B</b>) Segregation of (<b>A</b>) <i>LIPG</i> L130F-FS and (<b>B</b>) <i>GALNT2</i> D314A with elevated HDLc. For each individual, the individual ID, HDLc (in mmol/L) plus [HDLc percentile], and genotype are shown. Squares, Males; Circles, Females; Arrow, proband. Filled shape, HDLc≥90^th percentile; half-filled, HDLc between 80–89^th percentiles; empty shape, HDLc<80^th percentile. Slash = deceased. <b>C</b>) Percent of individuals in families with mutations at given HDLc percentiles or higher.</p

<i>LIPG</i>, <i>CETP</i>, and <i>GALNT2</i> mutations.

<p><i>LIPG</i>, <i>CETP</i>, and <i>GALNT2</i> mutations.</p

Phenotypes of family members with single <i>LIPG, CETP, and GALNT2</i> mutations.

a<p>, Average (SD) shown;</p>b<p>, N (%) shown.</p

Demographics of unrelated probands with extreme HDLc.

a<p>, Average (SD);</p>b<p>, N (%);</p>c<p>, Average (95% confidence interval).</p

Mutations identified in probands with high or low HDLc.

<p>A) Overview of the study design. <b>B–D</b>) Predicted mutation effects on <b>B</b>) LIPG, <b>C</b>) CETP, and <b>D</b>) GALNT2 proteins. Red sequence changes are novel, blue are previously described <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037437#pone.0037437-Edmondson1" target="_blank">[17]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037437#pone.0037437-deLemos1" target="_blank">[23]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037437#pone.0037437-Holleboom1" target="_blank">[28]</a>, and black is previously described in a subset of this cohort <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037437#pone.0037437-vanderSteeg1" target="_blank">[16]</a>.</p

Mutation frequencies and burden effects in probands.

a<p>, Two probands have rare <i>LIPG</i>+<i>GALNT2</i> variants.</p

Characterization of probands and families with multiple mutations.

<p><b>A</b>) Representative segregation of <i>LIPG</i> N396S and <i>ABCA1</i> IVS24+1G>C mutations. Filled shape, HDLc<15^th percentile; empty shape, HDLc≥15^th percentile. <b>B</b>) HDLc levels of individuals with <i>LIPG</i>+/−<i>ABCA1</i>, <i>LCAT</i>, or <i>LPL</i> mutations. Individuals with <i>LIPG</i> mutations alone are described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037437#pone-0037437-t004" target="_blank">Table 4</a>. Individuals with single <i>ABCA1</i>, <i>LCAT</i>, and <i>LPL</i> mutations are from an independent Dutch-Caucasian population (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037437#pone.0037437.s003" target="_blank">Tables S1</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037437#pone.0037437.s004" target="_blank">S2</a>, and S3 and data not shown). <b>C</b>) HDLc levels of individuals with mutations in <i>LIPG</i>, <i>GALNT2</i>, or <i>LIPG+GALNT2</i>. Individuals with single <i>LIPG</i> or <i>GALNT2</i> mutations are described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0037437#pone-0037437-t004" target="_blank">Table 4</a>.</p