Repro 33-36

Front 1

How do you increase N excretion in Hyperammonemia

Back 1

w/ Arg or citrulline, Na benzoate, Na phenylacetate, Na phenylbutyrate

Front 2

Biotinidase def

Back 2

– cleaves biotin peptides released in proteolytic degradation
– def -> seizures, ataxia, hypotonia, developmental delay, skin rash, alopecia
– tx kids w/ 5-20 free mg/day

Front 3

Aldurazyme

Back 3

(recombinant human iduronidase) for MPS1

Front 4

Naglazyme

Back 4

(recombinant human arylsulfatase B) forMPS VI

Front 5

Oncogenic potential of replication-competent retrovirus

Back 5

– Death
– Insertional mutagenesis
– Altered germ line
– Infections from infectious viral particles formed by recombination

Front 6

PKU incidence

Back 6

– 1/15,000 to 1/20,000 in US
– More common in N. European ancestry (carrier frequency is about 1/50)

Front 7

PKU inheritance pattern

Back 7

– AR w/ variable expression
– due to varying levels of enzyme activity and other epigenic effects that may modulate Phe (absorption in digestion, transport across the BBB)

Front 8

PKU mutations

Back 8

– Allelic heterogeneity
– over 400 mutations in the phenylalanine hydroxylase gene on 12q
– most are compound heterozygotes (two different mutations w/in the gene)

Front 9

Fetal intracranial hemorrhage types

Back 9

– Traumatic is subdural/subarachnoid hemorrhage
– Asphyxia is intraventricular hemorrhage

Front 10

TORCH, what do each of the organisms cause

Back 10

– Toxo, CNS damage and chorioretinitis
– Others are Listeria and Syphilis, CNS damage and liver dysfunction
– Rubella causes congenital heart and eye defects, CNS damage, neonatal hepatitis
– CMV, CNS damage, neonatal hepatitis, chorioretinitis
– Herpes, CNS damage, eye damage, neonatal hepatitis

Front 11

What is the most common fetal TORCH outcome

Back 11

Growth retardation and abnormalities of brain, eyes, liver, hematopoietic system and heart are most common

Front 12

RDS complications

Back 12

intraventricular hemorrhage, Patent ductus arteriosus, and Necrotizing enterocolitis – tx w/ Bronchopulmonary dysplasia and Rentrolental fibroplasias

Front 13

Marfans incidence

Back 13

1/10,000, 25% new mutations

Front 14

Marfans inheritance pattern

Back 14

AD, variable expression

Front 15

Marfans Mutations

Back 15

– Allelic heterogeneity
- various mutations within the FBN1 gene on chromosome 15q21
- protein is named fibrillin

Front 16

NFI incidence

Back 16

1/3000, 50% are new mutations

Front 17

NF1 inheritance

Back 17

AD, variable expression, nearly complete penetrance

Front 18

NF1 mutations

Back 18

Allelic heterogeneity, NF1 gene chromosome 17q, protein is neurofibromin

Front 19

Trisomy 13

Back 19

– 1/12,000 births
– Mean life expectancy 130 days
– 86% die during the first year
– Microcephaly, scalp defects, clefts, microphthalmia, polydactyly, cardiac defects, renal anomalies

Front 20

4p minus syndrome

Back 20

invovles cleft palate

Front 21

Wolf-Hirschorn syndrome

Back 21

involves cleft palate

Front 22

22q Deletion Syndrome

Back 22

– Cleft palate/submucous cleft palate, velopharyngeal insufficiency
– Conotruncal heart deftects
– Hypocalcemia
– Immune dysfunction (T-cells)
– Learning disabilities, psychiatric disorders

Front 23

Van der Woude Syndrome

Back 23

– Often very subtle clues, Lip pits
– IRF6 on 1q (TF)

Front 24

Popliteal pterygium syndrome

Back 24

– IRF6 on 1q (TF)
– same gene as Van der Woude syndrome

Front 25

Holoprosencephaly

Back 25

– abnormal morphogenesis of forebrain
– Etiology is heterogeneous
– maternal diabetes, trisomy 13, Smith-Lemli-Opitz syndrome (defect in cholesterol biosynthesis), SHH, TGIF, ZIC2, PTCH

Front 26

Native American Myopathy

Back 26

– AR condition in Lumbee
– cleft palate, congenital joint contractures, club feet, hypotonia and susceptibility to malignant hyperthermia with anesthesia

Front 27

Robin Sequence

Back 27

– micrognathia (small jaw), glossoptosis, cleft palate – Heterogeneity
– Malformational and deformational causes
– Connective tissue, chromosomal, oligohydramnios, neurogenic hypotonia

Front 28

Stickler syndrome

Back 28

– Robin sequence
– Myopia/retinal detachment
– Hearing loss
– Arthropathy
– Caused by mutations in Col 2A1, Col 11A1, Col 11A2 (lack eye findings)
– Locus heterogeneity refers to identical clinical symptoms caused by mutations at 2 or more different loci

Front 29

TF’s involved in cleft palate

Back 29

MSX1, FGFR1

Front 30

Array CGH is comparative genomic hybridization

Back 30

– Can detect deletions or duplications at 80-200 kb size using 800 clones spread throughout genome
– Average band size on metaphase chromosome 3.5-5 Mb

Front 31

Prader-Willi inheritance pattern

Back 31

Microdeletion, uniparental disomy or imprinting center defect

Front 32

Prader-Willi incidence

Back 32

1/10,000 to 1/15,000

Front 33

Prader-Willi mutations

Back 33

Absence of expression of the paternally contributed Prader-Willi/Angelman syndrome region on chromosome 15q11.2-q13