A Gene for Autosomal Recessive Symmetrical Spastic Cerebral Palsy Maps to Chromosome 2q24-25

1. A Gene for Autosomal Recessive Symmetrical Spastic Cerebral Palsy Maps to Chromosome 2q24-25 McHale, D.P., S. Mitchell, S. Bundey, L. Moynihan, D.A. Campbell, C.G. Woods, N.J. Lench, R.F. Mueller, & A.F. Markham. 1999. A Gene for Autosomal Recessive Symmetrical Spastic Cerebral Palsy Maps to Chromosome 2q24-25. American Journal of Human Genetics. 64: 526-532. Presented By: David Ocampo

2. Contents of Presentation • Background information on the topic of cerebral palsy (CP). • Go in-depth into the biological aspect of the topic.

3. Definition of Cerebral Palsy (CP) • Cerebral palsy is a static encephalopathy, which may be defined as a non-progressive disorder of posture and movement.

4. Statistics on CP • Approximately 1 in 1000 infants have some form of CP. • Approximately 50% of people with CP have spastic CP. • 25% have mental retardation. • 5-15% have some degree of sensorineural hearing loss.

5. Three Main Types Of CP • Spastic CP • Athetoid CP • Ataxic CP

6. Spastic Cerebral Palsy (CP) • Most common. • Account for 60% of all CP cases. • Muscles are tight and limited movement. • Stiff and jerky movements. • Difficult time holding and letting go of objects. • Difficult time moving around.

7. Athetoid CP • About 10 % of children • Is caused by damage to the cerebellum or basal ganglia • Develop involuntary movements • Problems maintaining posture for sitting and walking • Low muscle tone

8. Ataxic CP • Affects 5-10% of children. • Low muscle tone. • Poor coordination of movements. • Problems with balance and depth perception. • Take longer at writing and completing certain tasks.

9. What Factors Play a Role in the Causes Of CP? • Intrapartum problems. • Breech presentation. • Prematurity. • Small size for gestational size. • Multiple births. • Twins, triplets, etc. • Genetic factors (1-2%).

10. A Gene for Autosomal Recessive Symmetrical Spastic Cerebral Palsy Maps to Chromosome 2q24-25 • Recessive. • An allele or mutation that is only expressed phenotypically when it is present in the homozygous form.

11. What Is the Rationale of the Paper? • To locate the recessive genes that are responsible for spastic cerebral palsy.

12. How Was This Accomplished? • Analyzation of blood samples of eight families. • Different regions of the united kingdom. • Documentation of phenotypes were recorded. • Genome wide search was performed to identify a genetic locus responsible for spastic CP. • Usage of 290 polymorphic DNA markers.

13. Oldest boy Developmental delay Moderately retarded Spastic diplegia Brisk leg reflexes Plantar responses Sister Walk with support Speech delayed Moderately retarded Increased tone in legs Tendon reflexes Family 3

14. Clinical Features of Each Family

15. What Does Table 2 Tell Us? • Only certain markers were homozygous. • No interest in heterozygous.

16. Multipoint Analysis

17. Pedigree Chart

18. What Do the Results Mean? • Revealed that all four affected children in family 4 were homozygous for the marker D2S326.

19. Conclusion? • Cerebral palsy is poorly understood. • Difficult group of conditions to manage. • And although only 2% are in the genetic forms. • Further studying the genetics of CP should provide insight into both the cause of the disease and the development.

20. Questions?

21. Thank You!