Rnwk4- 5-2 Genetics Other

Front 1

What is prevalence of Unilateral Renal Agenesis?

Back 1

1:2000
--often incidental finding
--opp kidney can be enlarged
--at increased risk for kidney infections, stones, HTN and failure

Front 2

What is prevalence of Bilateral Renal Agenesis

Back 2

1 in 4,000 births

Front 3

Which trisomy's is Renal Agenesis assc/?

Back 3

Trisomy's
7, 10, 21, 22

Front 4

Which other 2 genetic dzz is Renal Agenesis assc/ ?

Microdeletions?

Back 4

Turners and Klinefelters

-Microdeltions: 22q11 & 11p13 (has WT1 gene for Wilms tumor)

think 11 and 13 are younger numbers than 11 and 22, and wilms tumor is in kidos

Front 5

Mutation in this gene causes complete agenesis or reduced size of kidney?

Back 5

SPRY2

Front 6

Name the (2 most?) essential genes in kidney development involved in signal transduction
--these are also proto-oncogenes)

Back 6

GDNF: glial cell derived neurophic factor
BMP4 (controles GDNF expr)

Others include: FOXD1, WT1, SPRY2 (nephrogenesis)

note WNT Famlly is important too: WNT4, WNT6, WNT7, WNT11

Front 7

This is the most common cause of an abdominal mass in a newborn?

Back 7

Multicystic Renal Dysplasia
-MRD
-palpable flank mass in otherwise healthy infant
-conn tissue cysts, no identifiable renal tissue in cysts

Front 8

As MRD results unilateral or bilateral, what is incidence?
Sex pref?

Back 8

1:3000 for MRD
--boys > girls

Front 9

What is Beckwith-Wiedemann Syndrome?

Back 9

Dont know, but its reported with MRD,
--so to is Trisomy 18

Front 10

What is COAL with regard to Cystinuria?

Back 10

Cystine
Ornithine
Arginine
Lysine

--note: Cystine = 2 sulfa linked Cysteines, which are metabs of Methionine

Front 11

What is Cystinuria?

Back 11

hereditary dzo of PCTs reabsorption of filtered Cystine and dibasic amino acids
--accums and precipitates b/c Cystine is weakly soluble in urine. So if not reabsorbed in PCT = stones in filtrate

--note: also absorption defic in intestines--not significant tho--ie non-essential aa's--ie serum levels of these aa's will be normal

Front 12

Heredity of Cystinuria?
Incidence in general population?

High risk population

Back 12

Auto Recessive
1:7000 general pop

1:15,000 in US
1:2500 in Libyan Jewish population

Front 13

What transporters and gene of similar nomen is resp for cystinuria?

Back 13

SoLute Carrer family of genes(SLC)
-Transporter has 2 subunits SLC3A1 and SLC7A9

Front 14

Which 2 subunits of SLC family and what disorder make up the transporter for absorption of these COAL aa's.

Which one is the actual channel?

Back 14

Cystinuria Transporter is 2 subunits from gene product: SLC3A1 & SLC7A9

SLC3A1 is the transmembrane Channel for the COALs
-7A9 is covalently bound and used to target it to luminal membrane

Front 15

What gene/chr and clinical findings are with...
a. Cystinuria type I (A)
b. Cystinuria type II,III (B) aka non-type I

Back 15

a. SLC3A1 ch2p1.3 all 4 AA's in high concentration in urine
b. SLC7A9 ch19q13.1 -elevated aa excretion, but variable intestinal absorption

Front 16

Tx options for Cystinuria?
1 specific to urine?

Back 16

alter urine pH to more alkaline
-note Animal Pr yields many Protons to urine= restrict Animal Prtein

--also things like fluids and reduced cystine intake

Front 17

This is ONE of the MOST common Hereditary Dzos
--12.5 million people affected?

Back 17

Polycystic Kidney Dz (PKD)
-growth of cysts, (large)
-

Front 18

What is most common form of PKD?

Back 18

Autosomal Dominant PKD
ADPKD
--gene freq = 1:1000, thus incidence is 1:400 to 1:1000
---most common life threatening dz (wiki)

--affects multiple Org. systems, >50% ESRD

--kidneys can become HUGE

Front 19

What is mechanism for cyst formation?

Back 19

abnormal cell growth, cyst begins as growth in Tubule, often due to fluid

--(may also occur in liver, spleen, panc.)

Front 20

Two types of PKD?
name genes involved

Back 20

usually due to NEW Mutation:
ADPKD and recessive one is ARPKD
a. ADPKD: common---involves PKD1 and PKD2 genes
b.ARPKD: Rare (1:10K -> 1:20K) PKHD1

Front 21

Note about ADPKD diagnosis?
What is main difference between ADPKD with abnormality in PKD1 (polycystin 1) vs. PKD2 (polycystin2)? (include info on chromosome as well as outcomes)

Back 21

a. PKD1- ch 16 shows in 85% of families with ADPKD, and End stage renal disease is 57 y/o
b. PKD2- ch 4 and end stag renal disease is 69 y.o.

Front 22

What sort of protein does PKD1 (aka Polycystin 1) encode

Back 22

(16th chrom)
~52kb DNA --> 4300 aa
=Integral Membrane Glycoprotein

Front 23

What do PKD1 and PKD2 do?
What disease family is the PKD genes a part of?

Back 23

Function Unkown:
PKD1: localized in cilia
PKD2: Calcium Channel in Cilia
---thought to control flow of fluid through the tubules

=Ciliopathies

Front 24

Sx of ADPKD?

Back 24

HTN (60-70%)
Kidney Infection (30-50%)
Hematuria (35-50%) often first sign
Stones (up to 20%)

Front 25

Sex difference in ADPKD with Liver Cysts?

Back 25

Incidence in equal in sexes

--Women exclusively get Very Large Cysts
---no Sx if not infected/pressed

Front 26

Name 3 other non-renal complications of PKD peeps?

Back 26

Heart Valve Dz
Colonic Diverticula
Abdominal Wall Hernias

Front 27

What is gene for ARPKD?
Location?
Makes what protein?
What type of mutation?

Back 27

PKHD1
--H for hepatic on Chrom 6.
--makes 16kb mRNA, 4K aa receptor like protein called Fibrocystin
- mutation is a missense one

Front 28

What Tx is being developed with rat model of PKD?

Back 28

TEMPO 3/4 Trial
-Tolvaptan Efficacy and Saftey in management of PKD Outcomes
--oral vasopressin V2 Rec Ibx

Front 29

Why do ADPKD most often occur in middle age or later in life?

Back 29

2- hit hypothesis