A homozygous mutation in @entity19498 in siblings with severe @entity717 and XXXX .

@entity462 @entity563 @entity72047 @entity508 @entity18242 @entity19498 @entity72048 @entity3929 @entity4242 @entity717 @entity1889
We performed exome analysis in two affected siblings with severe @entity717 ( @entity717 ), @entity4242 and @entity508 from an Ashkenazi Jewish consanguineous family. We identified only one rare variant, a missense in @entity19498 ( @entity72047 [ @entity72048 ]), that is homozygous in both siblings but not in any of their 11 unaffected siblings or their parents (Logarithm of odds, LOD score: 2.6). This variant is predicted damaging. We genotyped 450 controls of Ashkenazi Jewish ancestry and identified only 5 individuals who are heterozygous for this variant (minor allele frequency: 0.0056). @entity19498 ( @entity19498 ) encodes a transporter for neutral aminoacids such as @entity3929 , @entity563 , @entity462 and @entity1889 . @entity18242 is essential for neuronal survival and differentiation. Indeed, @entity18242 biosynthesis disorders affect brain development and cause severe @entity717 . In the brain, @entity18242 is synthesized in astrocytes but not in neurons. It has been proposed that @entity19498 mediates the uptake of @entity18242 into neurons and the release of glia-borne @entity18242 to neighboring cells. @entity19498 disruption may thus impair brain development and function by decreasing the levels of @entity18242 in neurons. The identification of additional families with mutations in @entity19498 would be necessary to confirm its involvement in @entity717 .
