Cerebellar hypoplasia and quadrupedal locomotion in humans as a recessive trait mapping to chromosome 17p.
نویسندگان
چکیده
BACKGROUND Congenital hereditary non-progressive hypoplasia of the cerebellum is a rare condition, frequently associated with other neuropathology such as lissencephaly. Clinically, the condition is associated with variable degrees of mental retardation, microcephaly, seizures, and movement disorders due to ataxia. In severe cases, patients are unable to ambulate independently, but nevertheless do use bipedal locomotion. METHODS AND RESULTS Here we present a family with seven affected members, five of whom never learned to walk on two legs but have fully adapted to quadrupedal palmigrade locomotion. These subjects show signs of cerebellar ataxia and are mentally retarded. MRI analysis demonstrated hypoplasia of the cerebellum and the cerebellar vermis as well as a small nucleus dentatus and a thin corpus callosum but no other malformations. We show, by a genome-wide linkage scan, that quadrupedal locomotion is a recessive trait linked to chromosome 17p. CONCLUSIONS Our findings have implications for understanding the neural mechanism mediating bipedalism, and, perhaps, the evolution of this unique hominid trait.
منابع مشابه
Homozygosity mapping and targeted genomic sequencing reveal the gene responsible for cerebellar hypoplasia and quadrupedal locomotion in a consanguineous kindred.
The biological basis for the 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 17p13.1-1...
متن کاملMutations in the very low-density lipoprotein receptor VLDLR cause cerebellar hypoplasia and quadrupedal locomotion in humans.
Quadrupedal gait in humans, also known as Unertan syndrome, is a rare phenotype associated with dysarthric speech, mental retardation, and varying degrees of cerebrocerebellar hypoplasia. Four large consanguineous kindreds from Turkey manifest this phenotype. In two families (A and D), shared homozygosity among affected relatives mapped the trait to a 1.3-Mb region of chromosome 9p24. This geno...
متن کامل"Devolution" of bipedality.
Ozcelik et al. (1) report mutations in very-low-density lipoprotein receptor (VLDLR) that are associated with quadrupedal gait. They propose a pivotal role for VLDLR in the transition from quadrupedal to bipedal locomotion in man. VLDLR is a key regulator of cerebellar development in vertebrates (2). All VLDLR mutations reported to date result in disequilibirium syndrome (DES) with cerebellar h...
متن کاملCA8 Mutations Cause a Novel Syndrome Characterized by Ataxia and Mild Mental Retardation with Predisposition to Quadrupedal Gait
We describe a consanguineous Iraqi family in which affected siblings had mild mental retardation and congenital ataxia characterized by quadrupedal gait. Genome-wide linkage analysis identified a 5.8 Mb interval on chromosome 8q with shared homozygosity among the affected persons. Sequencing of genes contained in the interval revealed a homozygous mutation, S100P, in carbonic anhydrase related ...
متن کاملReply to Herz et al. and Humphrey et al.: Genetic heterogeneity of cerebellar hypoplasia with quadrupedal locomotion.
Reply to Herz et al. and Humphrey et al.: Genetic heterogeneity of cerebellar hypoplasia with quadrupedal locomotion Mutations in the very low-density lipoprotein receptor VLDLR are responsible for cerebellar hypoplasia with qua-drupedal gait (1). The most likely mechanism leading to this phenotype is that VLDLR deficiency in the brain at a key stage of development precludes the normal formatio...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of medical genetics
دوره 43 5 شماره
صفحات -
تاریخ انتشار 2006