In this document, we will describe and analyze the Rhombencephalosynapsis. It is a congenital cerebellar malformation belonging to a group of anomalies defined as Cerebellar and Brainstem Congenital Defects (CBCD). In particular, we will investigate its partially known causes. The Rhombencephalosynapsis is characterized by agenesis of the cerebellar vermis, which leads to the fusion of the hemispheres, the dentate nuclei, and the superior cerebellar peduncles. This malformation causes severe symptoms: swallowing difficulties, muscle hypotonia, delayed motor acquisition, spastic quadriparesis, dysarthria, gait ataxia, abnormal eye movements, nystagmus, and stereotyped head movements. In some cases, hydrocephalus and convulsions have been observed. Through ultrasound and fetal magnetic resonance, it is possible to diagnose Rhombencephalosynapsis in the early pregnancy stages. Nevertheless, despite the severity of the disease, its causes have not been identified. The reason is due to its sporadic nature. Nowadays, the specific genetic and etiological factors responsible for cerebellar malformation are still unknown. Therefore, we will propose an in-depth study to identify the genetic variant responsible for the phenotype. We have analyzed twelve patients with a clinical and neuroradiological diagnosis of Rhombencephalosynapsis by using Molecular Biology techniques. The aim of the study is to identify new causative genes for CBCDs through the aforementioned analyzes. Specifically, we will examine the MN1 gene by exploiting the automatic Sanger sequencing. Finally, we will report the variants we have founded.
Nel presente documento verrà descritta e analizzata la Romboencefalosinapsi, malformazione cerebellare congenita facente parte di un ampio gruppo di anomalie definite come difetti del cervelletto e del tronco encefalo (Cerebellar and Brainstem Congenital Defects, CBCD). In particolare, ne saranno investigate le cause ad oggi solo in parte note. La Romboencefalosinapsi è caratterizzata da agenesia del verme cerebellare, che porta alla fusione degli emisferi, dei nuclei dentati e dei peduncoli cerebellari superiori. Tale malformazione causa gravi sintomi, quali: difficoltà nella deglutizione, ipotonia muscolare, sviluppo motorio ritardato, quadriparesi spastica, disartria, atassia dell’andatura, movimenti oculari anormali, nistagmo e movimenti stereotipati della testa. In alcuni casi si sono osservati anche idrocefalo e convulsioni. Tramite ecografia e risonanza magnetica fetale è possibile diagnosticare la Romboencefalosinapsi nelle prime fasi della gravidanza. Tuttavia, nonostante la gravità della patologia, vista la sporadicità della sua manifestazione, non sono ancora state individuate le cause della stessa. Ad oggi, i precisi fattori genetici ed eziologici responsabili della malformazione cerebellare sono ancora sconosciuti. Pertanto, si propone uno studio approfondito atto a identificare la variante genetica responsabile del fenotipo. Sono quindi analizzati dodici pazienti, aventi diagnosi clinica e neuroradiologica di Romboencefalosinapsi, impiegando tecniche di Biologia Molecolare. L’obbiettivo dello studio è identificare nuovi geni causativi delle CBCD attraverso le suddette analisi. Nello specifico, verrà esaminato il gene MN1 attraverso l’utilizzo del sequenziamento automatico Sanger. Infine, saranno riportare le varianti riscontrate.
La Romboencefalosinapsi: analisi genetico-molecolare di 12 individui affetti.
MARCHETTI, BARBARA
2019/2020
Abstract
In this document, we will describe and analyze the Rhombencephalosynapsis. It is a congenital cerebellar malformation belonging to a group of anomalies defined as Cerebellar and Brainstem Congenital Defects (CBCD). In particular, we will investigate its partially known causes. The Rhombencephalosynapsis is characterized by agenesis of the cerebellar vermis, which leads to the fusion of the hemispheres, the dentate nuclei, and the superior cerebellar peduncles. This malformation causes severe symptoms: swallowing difficulties, muscle hypotonia, delayed motor acquisition, spastic quadriparesis, dysarthria, gait ataxia, abnormal eye movements, nystagmus, and stereotyped head movements. In some cases, hydrocephalus and convulsions have been observed. Through ultrasound and fetal magnetic resonance, it is possible to diagnose Rhombencephalosynapsis in the early pregnancy stages. Nevertheless, despite the severity of the disease, its causes have not been identified. The reason is due to its sporadic nature. Nowadays, the specific genetic and etiological factors responsible for cerebellar malformation are still unknown. Therefore, we will propose an in-depth study to identify the genetic variant responsible for the phenotype. We have analyzed twelve patients with a clinical and neuroradiological diagnosis of Rhombencephalosynapsis by using Molecular Biology techniques. The aim of the study is to identify new causative genes for CBCDs through the aforementioned analyzes. Specifically, we will examine the MN1 gene by exploiting the automatic Sanger sequencing. Finally, we will report the variants we have founded.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/12320