Notez

---Glutaric Acid uria:

Large head, fever, dystonic movt ---glutaric acid uria
Sympt appear during ac illness
Mri..basal ganglia involved, bat wing appearance
Treatment....carnitine

 Neuropathy where axonal muscles are not involved: CMT

pleiotropy: single gene may cause multiple phenotypic expressions

+Criteria for muscular dystrophy:

 primary myopathy

Genetic bases

Progressive

Degeneration and death of muscle fiber

+Self injury inflicting 

1. Smith mengnis syndrome

2.lysh nyhan

3.PKU

4.tyrocenemia type3

+ D/d Marfan syndrome

Homocysteinuria

+ Double malleolus seen in Ricketts

+ Depressed nasal bridge and prominent eyes and split distal phalak seen in Robinow syndrome

+Advanced paternal age is defined as age of father more than 40yrs, it increases the risk of genetic abnormalities by 0.5 to 1%

+Foetal microarray testing adds to 10% more of information as we get from karyotype

+With consanguinity, the risk of genetic disorders is increased by 1.5% over the general population risk

+In general population the carrier risk of SMA is 1in50

+Thallessmia carriership in sindhis is 5%

+15% risk of so an in every preg

+ Early IUD with hydrops cause may be Turner syndrome

+Corneal clouding in MPS: seen in 1,3,4

Not seen in 2

Mps1...all typical phenotype ( course face, corneal clouding, hirsuitism, joint contracture, protruding belly, hsm)

Mps2...no corneal clouding, x linked 

Mps3... behaviour problems 

Mps4 ...skeletal. Amomalies, short stature, hsm, no jt contracture infact lax jt.

+ Adult onset tremoulsness.....Rule out SMA first

+Human genome is 3billion bp, out of which only 1% contain genes.

+ Region in gene of longer than 500kb with no ORF are k/a desserts. 20% of human genome contains deserts.

+Human genome contains sequence that do not have coding function but still conserved through out species, this evolutionary conservation is certainly higher than the background level, which mandate them to be important.

+Repeated sequence accounts for more than 50% of genome, 45%of which are transposon

+Transposons are the sequence in genome that are mobile that is they are able to transport themselves to other region in genome.

Significance: while moving themselves transposons can transfer other gene sequence with them, hence are major source of mutation. In genome.

+ Most of the mutation in hbb are in 100 to 400

One common polymorphism is seen in almost all samples of hbb k/a cat polymorphism

+Status rica

For discrete or qualitative variable do chi square test

For continue us or quantitative variable do student t test

To address association in two variable do odd ratio

Linkage disequilibrium

Hardy Weinberg law

+ATRX gene...Alpha thal and x linked mental retardation, wile somatic mutation of ATRX cause myelodysplasia syndrome (MDS)

+ Stickler syndrome: flat face, mid face hypoplasia, prominent eyes, 50% have Pierre robin's sequence, spondylosis epiphyseal dysplasia is common 

Do not have intellectual disability

May have arthropathy or joint pain

+ Tuberous sclerosis treatment:  everolimus (a rapalog) is currently approved by the FDA (U.S. Food and Drug Administration) and EMA (European Medicines Agency) for tumours associated with tuberous sclerosis complex (renal angiomyolipoma and subependymal giant cell astrocytoma), the use of these drugs for treating other symptoms of the condition has yet to be established. 

+ Patient with tuberous sclerosis, may present with autistic behaviour similar to fragile x syndrome.....So always look for tuberous signs in such cased

Dd blue sclera: osteogenesis. Imperfecta, silver Russel syndrome, pyknodysostodos,

+Situs inversus, important cause is primary colliery dyskinesia

+APP7A   .....     Menkes dis

ATP7B.     ......    William dis

+Hot spot for DMD....Exon 5-11 and 44- 61

+ Lyso GB1, is a specific market for Gaucher disease

+ Recurrence risk cleft palate..5%

+ In sulfite oxidase def like molybdenum co A Def..... progression is rapid, usually normal at birth but within 1mth may become severe with severe cerebral atrophy, microcephaly...normal HC at birth

+ Asuragen kit for fragile X syn

+syndrome of Cong diaphragm hernia*

Simpson-Golabi-Behmel syndrome, Denys-Drash syndrome, spondylocostal dysostosis, craniofrontonasal syndrome, Cornelia de Lange syndrome and Marfan syndrome

+ Primary microcephaly: most common gene ASPM gene

+ Galactokinase Def cause only congenital cataract, chances of getting other symptoms of galactosemia are less, treatment in this is debatable including strict diet restrictions

Classical galatossemia is Galt Def, more common, strict diet restrictions advised

+ASS, ASL, arginase enzymes from Urea cycle can be seen in CBS sample

+ Software for Agilent...cytogenomics

For Affymetrix....Chas

+ Subtelomeric MLPA probes serves the same purpose as FISH probes but are cheaper hence preferred

+Low PAPP-A...less than 0.5...associated with Iugr (specially if less than 0.25), preterm, pregnancy loss before 20 wks and pre eclampsia.

+ Protein structuring software....raptor x, pymol.org, si mol

+Normal female with b/l inguinal hernia....think of male with 5alpha reductase def

+ If mother not carrier of deletion.....chances of recurrence is 8 per in subsequent pregnancy

,,+Close dd for mitochondrial encephlo is acute necrotizing encephlopathy

For mito...big50 given

+ MELAS MRI: multiple demelinating patches, on repeating after few month they disappear and reappear in other are

+ Acroparasthsiae in fabry treated by Carbamazipi 

+Vertical supranuclear vmgaze palsy....initially can not look down than up then horizontal saccad then vertical saccda so in the end of NPC absent eye movt

Soliris...treatment for pnh

Ciniryza