שינוים גנומיים בשיתוק מוחין קריפטוגני
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Transcript of שינוים גנומיים בשיתוק מוחין קריפטוגני
Microarray Analysis for Identifying Genetic causes for Idiopathic CP-a Preliminary Study Reeval Segel1*, Hilla Ben-Pazi2*, Sharon Zeligson1, Aviva
Fatal-Valevski3, Adi Aran2, Varda Gross2, Nira heinbaum3, Dorit Shmueli4, Dorit Lev5, Shira Perlberg1, Ephrat Levi-Lahad1
1Medical Genetics Institute Shaare Zedek Medical Center, Jerusalem;2Pediatric Neurology Unit, Shaare Zedek Medical Center, Jerusalem;3 Pediatric Neurology Unit, Dana Children’s Hospital, Tel-Aviv;4Jerusalem Child Development Center, Clalit, Jerusalem;5 Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Holon;
Genetic factors in CP
“Genomic insights into the causes and classification of the cerebral palsies”
Moreno-De-Luca et al. Lancet Neurol 2012
Complex neurological disorder There are instances the etiology is clear cut other cases- no etiology is apparent
Aim-
1) To identify the non- acquired CP
2) To identify genomic rearrangements in individuals
with non- acquired CP by microarray analysis.
Rationale for sequences Sequence
“Single incident caused a chain of events
leading to a syndromatic appearance” i.e. Pierre Robin sequence
Similar to epilepsy (ILAE)- Multi level axes Not each case can be categorized
event
MethodsMethods Summary letters reviewed according to 3
axes: History Anatomic distribution Imaging
Classified accordingly into 3 sequences Hypoxic- ischemic sequence Hemispheric lesion sequence Periventricular lesion sequence
computerized summary letters reviewed.
Each letter was searched for parameters ~ 1-2 minutes per case.
Hypoxic Ischemic SequenceHistory:
• Term infant• Hypoxia-ischemia
• Full resuscitation • Apgar <7 at 5 min • Sarnat grade >2
Anatomic distribution:• QuadriplegiaImaging: • Bihemispheric • Deep grey matter injury• Normal
Hemispheric Lesion SequenceHistory: • Term infantAnatomic distribution: • hemiplegia Imaging: • Hemispheric lesion
• Stroke• Tumor• AVM
Periventricular Leucomalacia- PVL SequenceHistory: • Prematurity of 24-34WAnatomic distribution: • Di, Hemi, quadriplegia Imaging: • PVL
RESULTS
(n=195)
Preliminary- Genetic Results
47 cases 24 had 35 genomic rearrangements
(GR) 9 de novo 10 inherited 16 ongoing
7 had multiple GR
Startle שנים- 13ח.פ. בת היפוטוניה אקסיאלית ודיסטוניה בגפיים קוגניציה שמורה יחסית
.אך ישנה ירידה לאחרונה בעיות שינהמיקרוצפליהקשיי נשימהdel22q11.21. 2.8Mb
היפוקלצמיה
היפוקלצמיה
SOBIN et al 2005
להורים אשכנזים לא קרובי 2/4 משפחה
שנים10בן ,דיסמורפי, שפה שסועהשיער שיבהלאחרונה דיסטוניה
שנים5בן ספסטיק דיפלגיה
מתקדמתADHD
Different deletion
-Any ideas?
Different deletion
-Any ideas?
5.2 Mb Del 2 p23.1-p22.2
Spastin
1.96Mbdel19q13.12mitochondrial enzymesZinc fingers unknown
A whole deletion would be missed
A whole deletion would be missed
Thanks SZMC:
Reeval Segel, Sharon Zeligson, Shira Perlberg, Ephrat Levi-Lahad
Adi Aran, Varda Gross DANA:
Aviva Fatal-Valevski, Nira Sheinbaum CDC Clalit
Dorit Shmueli Wolfson
Dorit Lev