Numerous genes are involved in @entity1 growth regulation. Recently, autosomal-recessive inherited variants in centrosomal proteins have been identified in @entity20208 , @entity8125 , or @entity20208 osteodysplastic primary dwarfism. Common hallmarks of these syndromic forms are severe @entity851 and @entity4242 . In a consanguineous family with two affected @entity1 with severe @entity851 and normocephaly, we used homozygosity mapping and next-generation sequencing to identify a homozygous @entity54184 variant. @entity54184 is a major protein for microtubule assembly during mitosis. High-expression levels in the somite boundaries of @entity3392 suggested a role in growth and body segment patterning. The identified variant affects binding sites of kinases necessary for dynamic instability of microtubule formation. We found centrosome amplifications in mitotic fibroblast cells in vivo and in vitro. These numeric centrosomal aberrations were also present during interphase resulting in aberrant ciliogenesis. Furthermore, affected cells showed a dysfunction of the microtubule-dependent assembly of the Golgi apparatus, indicated by a significant lack of compactness of Golgi membranes. These observations demonstrated that @entity54184 mutations contribute to the clinical spectrum of centrosomal defects and confirmed the complex role of a centrosomal protein in centrosomal, ciliary, and Golgi regulation associated with severe @entity851 .

XXXX -Dependent Regulation of Microtubule Formation Affects Centrosome, Cilia, and Golgi Architecture as a Central Mechanism in Growth Regulation.

@entity1 :: ('9606', 'Species') :: ['children', 'human'] @entity851 :: ('MESH:D006130', 'Disease') :: ['growth retardation', 'short stature'] @entity8125 :: ('MESH:C579935', 'Disease') :: ['primary microcephaly'] @entity20208 :: ('MESH:C537533', 'Disease') :: ['microcephalic', 'Seckel syndrome'] @entity54184 :: ('4134', 'Gene') :: ['MAP4'] @entity4242 :: ('MESH:D008831', 'Disease') :: ['microcephaly'] @entity3392 :: ('7955', 'Species') :: ['zebrafish']
@entity54184 :: (4134,Gene) :: ['MAP4']
