TY  - JOUR
A1  - Gulsuner, Suleyman
A1  - Tekinay, Ayse B
A1  - Doerschner, Katja
A1  - Boyaci, Huseyin
A1  - Bilguvar, Kaya
A1  - Unal, Hilal
A1  - Ors, Aslihan
A1  - Onat, Onur Emre
A1  - Atalar, Ergin
A1  - Basak, A Nazli
A1  - Topaloglu, Haluk
A1  - Kansu, Tulay
A1  - Tan, Meliha
A1  - Tan, Uner
A1  - Gunel, Murat
A1  - Ozcelik, Tayfun
T1  - Homozygosity mapping and targeted genomic sequencing reveal the gene responsible for cerebellar hypoplasia and quadrupedal locomotion in a consanguineous kindred
Y1  - 2011/09/01 
JF  - Genome Research 
JO  - Genome Research 
DO  - 10.1101/gr.126110.111 
SP  - gr.126110.111 
UR  - http://genome.cshlp.org/content/early/2011/09/01/gr.126110.111.abstract 
N2  - The biological basis for development of the cerebro-cerebellar structures required for posture and gait in humans is poorly understood. We investigated a large consanguineous family from Turkey exhibiting an extremely rare phenotype associated with quadrupedal locomotion, mental retardation and cerebro-cerebellar hypoplasia, linked to a 7.1 Mb region of homozygosity on chromosome 17p13.1-13.3. Diffusion weighted imaging and fiber tractography of patient brains revealed morphological abnormalities in the cerebellum and corpus callosum, in particular atrophy of superior, middle, and inferior peduncles of the cerebellum. Structural magnetic resonance imaging showed additional morphometric abnormalities in several cortical areas, including corpus callosum, precentral gyrus and Brodmann areas BA6, BA44, and BA45. Targeted sequencing of the entire homozygous region in three affected individuals and two obligate carriers uncovered a private missense mutation, WDR81 p.P856L, which co-segregated with the condition in the extended family. The mutation lies in a highly conserved region of WDR81, flanked by an N-terminal neurobeachin domain and C-terminal WD40 beta-propeller domains. WDR81 is predicted to be a transmembrane protein. It is highly expressed in the cerebellum and corpus callosum, in particular in the Purkinje cell layer of the cerebellum. WDR81 represents the third gene, after VLDLR and CA8, implicated in quadrupedal locomotion in humans. 
ER  -