MUTATIONS IN DSTYK AND DOMINANT URINARY TRACT

MALFORMATIONS

C a r o l i n a C a r v a j a l M i r a n d a C h r i s t i a n S á n c h e z v a l e n c i a

U P B - Fa c u l t a d d e M e d i c i n aM e d e l l í n

S. Sanna-Cherchi, R.V. Sampogna, N. Papeta, K.E. Burgess, S.N. Nees, B.J. Perry,M. Choi, M. Bodria, Y. Liu, P.L. Weng, V.J. Lozanovski, M. Verbitsky, F. Lugani,R. Sterken, N. Paragas, G. Caridi, A. Carrea, M. Dagnino, A. Materna-Kiryluk,G. Santamaria, C. Murtas, N. Ristoska-Bojkovska, C. Izzi, N. Kacak, B. Bianco,

S. Giberti, M. Gigante, G. Piaggio, L. Gesualdo, D. Kosuljandic Vukic,K. Vukojevic, M. Saraga-Babic, M. Saraga, Z. Gucev, L. Allegri, A. Latos-Bielenska,D. Casu, M. State, F. Scolari, R. Ravazzolo, K. Kiryluk, Q. Al-Awqati, V.D. D’Agati,

I.A. Drummond, V. Tasic, R.P. Lifton, G.M. Ghiggeri, and A.G. Gharavi

Introducción

Urinary malformation: Alteration of the shape of the organs in the urinary tract caused by a development desorder.

23% of birth defects.

40-50% pediatric,7% of adult

cases(ESRD)

URINARY TRACT MALFORMATIONSKidney

o Renal agenesis: Unilateral, Kidney is either absent or

undeveloped.

o Renal hypoplasia: Small kidney with the other one larger than

normal

o Renal dysplasia and multicystic kidney:Normally only one kidney irregularly lobulated

mass of cysts.

o Ectopic kidney: Not ascend properly.

URINARY TRACT MALFORMATIONSUreter and ureteropelvic

junction

Ureteral atresia:

Ureter may be absent or fail to extend to the bladder

Duplication of the ureter:

Most common,recurrent urinary tract infections.

Obstructed mega-ureter:

Obstruction at the ureterovesical junction.

URINARY TRACT MALFORMATIONSBladder

Bladder exstrophy:

Absence of the anterior wall of the bladder, with ureters delivering urine into the lower abdomen.

Persistent urachus:

Draining umbilical sinus and can become infected.

Contracture of the bladder neck:

Causes reflux, bladder diverticula and irritable bladder.

MUTATIONS IN DSTYK

This gene encodes a dual serine/threonine and tyrosine protein kinase which is expressed in multiple tissues. It is thought to function as a regulator of cell death.

DSTYK

kinase

ERK FGF-inducedtranscriptional activity

MALFORMATION

FG2

Objetivo

Identify independent mutations in DSTYK in patients with congenital abnormalities of the kidney and urinary tract.

Materiales y métodos

Genotipificacion:determina genotipo. Diferencias en movilidad de los fragmentos de ADN en geles, amplificación diferencial por PCR, o la hibridación.

Secuenciacion:determinación del orden de los nucleótidos en un oligonucleótido de ADN.

Inmortalizacion de linfocitos: cultivos proliferación ilimitada + células mas renovación, mediante transformación por tto químico o una infección viral.

17 Miembros familiares

Inmunohistoquimica: uso de anticuerpo , marcado enzima (sut. Visible) Test: ratones,1 riñon(3meces)

Inmunofluorescencia:anti-RIPS,FGF (Factor de Cto fibroblastico) FGF1,2,anti-acuaporina 2, anti-E-Cadherina

Pez Zebra Knock down: modificacion para expresión reducida de genes insertando pequeños fragmentos u oligonucleótido con secuencia complementaria.

Morpholino------Bloquea DSTYK

Western blot: detectar proteínas específicas en una muestra determinada

Resultados

Discussion

Reference What they said? Agree / Desagre

e

Schedl A.

“The development of the kidney and the urinary tract is orchestrated by a series of inductive signals between the metanephric mesenchyme and the ureteric bud, and any disruption of this reciprocal signaling results in developmental defects”.

Sanna-Cherchi S et

al

“The diversity of signaling pathways in nephrogenesis explains the significant locus heterogeneity of congenital abnormalities of the kidney and urinary tract”.

Bates CM.

“Different combinations of FGF ligands are expressed in the ureteric bud, metanephric mesenchyme, and renal stroma”.

Guillemot F et al

Engagement of the FGF receptor results in autophosphorylation and activation of the intracellular mitogen-activated protein kinase cascade, ultimately resulting in the production of pERK, the main effector of the FGF transcriptional program.

Conclusions

Its very important to know the changes that can happen to DSTYK gene because helps to diagnose abnormalities of the kidney and urinary tract.

The exome sequencing is an important tool for diagnosis in patients with genetic pathologies heterogeneous.The loss of fibroblast growth factor FGF and developmental defects in multiple organs is indicative of the presence of gene DSTYK.Any alteration in the signaling process that

induces renal embryonic tissue develops has as results pathological defect in the formation of this organ and routes of excretion.

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Mapas conceptuale

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