Genetic Disease With Common Mutations - For Gc Board Exam

Front 1

achondroplasia - gene and common mutations?

Back 1

FGFR3
gly380Arg - 1138G>A (98%), 1138G>C (2%)
GoF mutation that causes consitutive activation of receptor, which inhibits proliferation of chondrocytes at growth plate

Front 2

gaucher - gene, AJ mutation and carrier rate?

Back 2

GBA @ 1q21
AJ: N370S - 1/18 carrier rate

Front 3

hemophilia A - gene, common mutation

Back 3

F8 @ Xq28
allelic heterogeneity, but most common mutation is an intron 22 gnee inversion accounts for 1/2 of severe cases

Front 4

factor V leiden - gene, mutation

Back 4

F5, Arg 506Gln
2-15% of Europeans

Front 5

hemochromatosis - gene, 2 common mutations and their frequencies

Back 5

HFE @ 6p21.3
Cys282Tyr - 90-95% of pt are homozygous
5-10% are compound hets for Cys282Tyr and His63Asp

carrier rate: 11% of whites carry Cys282Tyr
27% of " carry His63Asp

Front 6

BRCA1 AJ mtn

Back 6

185delAG (1% carrier rate in AJ)
5382insC (0.4% carrier rate in AJ)

Front 7

BRCA2 AJ mtn

Back 7

6174delT (1.2% carrier rate in AJ)

Front 8

fanconi anemia AJ mtn

Back 8

FancC IVS4+4A>T
1/89 carrier rate

Front 9

bloom AJ mtn

Back 9

BLM @ 15q26.1
2281del6ins7
1/107 carrier rate

Front 10

diastrophic dysplasia - gene, mutations

Back 10

SLC26A2 @ 5q32-33.1
5 common mutations:
R279W
IVS1+2T>C
delV340
R178X
C653S

Front 11

sickle cell - gene, mutation

Back 11

HBB @ 11p15.5
Glu6Val

Front 12

Hb C - gene, mutation

Back 12

HBB @ 11p15.5
Glu6Lys

Front 13

prothrombin - gene, mutation

Back 13

F2 @ 11p11.2-12 (?)
G20210A

Front 14

MTHFR - gene, mutation

Back 14

MTHFR
C677T - 11-33% of caucasian population

Front 15

Crouzon - gene, mutation

Back 15

FGFR2 @ 10q26
A391E

Front 16

Apert - gene, mutation

Back 16

FGFR2 @ 10q26
P253R
S252W

Front 17

MYH - associated polyposis - gene, mutations

Back 17

MYH @ 1p
Y165C
G382D

Front 18

MCAD - gene, mutation

Back 18

ACADM (medium chain acyl CoA dehydrogenase) @ 1p31
K304E

Front 19

carnitine palmitoyl-transferase deficiency - gene, mutation

Back 19

CPTII @ 1p32
S113L (60%)

Front 20

isovaleric acidemia - gene, mutation

Back 20

IVD @ 15q14
A282V (50%)

Front 21

Canavan AJ mtn - gene, mtn

Back 21

ASPA @ 17pter
A285E
Y231X

Front 22

galactosemia - gene, classical mutation, duarte variant

Back 22

GALT @ 9p13
classical: Q188R (70%)
Duarte: N314D

Front 23

pallister-hall - gene, mutations

Back 23

GLI3 @ 7p13
2023delG
2012delG

Front 24

Progeria (hutchinson-gilford syn) - gene, mutation

Back 24

LMNA @1q21.2
G608G (1824C>T) -- activates a cryptic splice site.

Front 25

NARP and Leigh

Back 25

mtDNA T8993G

Front 26

LHON

Back 26

mtDNA 1178A>G in ND4 subunit of complex I is most common mtn

14459T>A, ND1 subunit - most severe mtn, less sex bias

Front 27

MERRF

Back 27

tRNAlys point mutations, most common is 8344A>G

Front 28

MELAS

Back 28

tRNAlue, most common is 3243A>G

Front 29

deafness - mitochondrial

Back 29

1555A>G in 12S rRNA
7445A>G mtn in 12S rRNA

Front 30

CPEO - chronic progressive external opthalmoplegia

Back 30

the MELAS mtn - 3243A>G in tRNAleu
large dels like KSS (5kb del)

Front 31

Kearns-Sayre syndrome

Back 31

~5kb deletion

Front 32

Tay Sachs AJ allele and carrier rate

Back 32

1/27 carrier rate
3 alleles: 4bp insertion - 80% of alleles, exon 12 splice mtn 10-15%, gly269ser 2-3%

Front 33

Alkaptonuria
HGD

Back 33

AR
AA disorder, in phe/tyr pathway
homogentisic acid builds up
excreted in urine - oxidized - dark
ochronosis (>30yo) - build up and darkening of connective tissue, cartilage
arthritis (>20yo)
also: renal stones, prostate stones, aortic or mitral valve calcification
tests: urinalysis of HGA levels using GC-MS