Missense mutation in the ATPase, aminophospholipid transporter protein ATP8A2 is associated with cerebellar atrophy and quadrupedal locomotion
European Journal of Human Genetics (2013) 21, 281–285
Onur Emre Onat, et al.
Cerebellar ataxia, mental retardation and dysequilibrium syndrome is a rare and heterogeneous condition.
We investigated a consanguineous family from Turkey with four affected individuals exhibiting the condition.
Homozygosity mapping revealed that several shared homozygous regions, including chromosome 13q12.
Targeted next-generation sequencing of an affected individual followed by segregation analysis, population screening and prediction approaches revealed a novel missense variant, p.I376M, in ATP8A2.
The mutation lies in a highly conserved C-terminal transmembrane region of E1 E2 ATPase domain.
The ATP8A2 gene is mainly expressed in brain and development, in particular cerebellum.
Interestingly, an unrelated individual has been identified, in whom mental retardation and severe hypotonia is associated with a de novo t(10;13) balanced translocation resulting with the disruption of ATP8A2.
These findings suggest that ATP8A2 is involved in the development of the cerebro-cerebellar structures required for posture and gait in humans.
Keywords: ATP8A2; cerebellar hypoplasia; targeted next-generation sequencing; quadrupedal locomotion; CAMRQ
Uner tan syndrome: history, clinical evaluations, genetics, and the dynamics of human quadrupedalism.
Open Neurol J. 2010 Jul 16;4:78-89.
This review includes for the first time a dynamical systems analysis of human quadrupedalism in Uner Tan syndrome, which is characterized by habitual quadrupedalism, impaired intelligence, and rudimentary speech. The first family was discovered in a small village near Iskenderun, and families were later found in Adana and two other small villages near Gaziantep and Canakkale. In all the affected individuals dynamic balance was impaired during upright walking, and they habitually preferred walking on all four extremities. MRI scans showed inferior cerebellovermian hypoplasia with slightly simplified cerebral gyri in three of the families, but appeared normal in the fourth. PET scans showed a decreased glucose metabolic activity in the cerebellum, vermis and, to a lesser extent the cerebral cortex, except for one patient, whose MRI scan also appeared to be normal. All four families had consanguineous marriages in their pedigrees, suggesting autosomal recessive transmission. The syndrome was genetically heterogeneous. Since the initial discoveries more cases have been found, and these exhibit facultative quadrupedal locomotion, and in one case, late childhood onset. It has been suggested that the human quadrupedalism may, at least, be a phenotypic example of reverse evolution. From the viewpoint of dynamic systems theory, it was concluded there may not be a single factor that predetermines human quadrupedalism in Uner Tan syndrome, but that it may involve self-organization, brain plasticity, and rewiring, from the many decentralized and local interactions among neuronal, genetic, and environmental subsystems.
MRI; PET; Uner Tan syndrome; balance; cerebellum; facultative quadrupedal locomotion; human quadrupedalism; human.; intelligence; locomotion; self-organization; speech; systems theory
Mutations may make humans walk on all fours
Genetic analysis revives dispute about why some humans are quadrupeds.
Nature. 2 June 2008
The existence of quadruped humans was first publicized by a 2006 British television documentary about a Turkish family in which several adults walk on all fours. Those with the condition also suffer from mental retardation and poor balance.
Since the broadcast, others with the condition have come to light, including one family in Brazil and another in Iraq.
The affected individuals all move by what is called a ‘bear crawl’: resting their weight on their wrists and keeping their legs straight and their rears lifted in the air.
quadruped individuals in two of the families carry a mutation in a gene called VLDLR.
The gene encodes a protein called very low-density lipoprotein receptor, which is required for proper neural development.
Baby born with partial brain
October 28, 2015