Ignite Creation Date:
2024-05-05 @ 9:23 PM
Last Modification Date:
2024-10-26 @ 10:03 AM
Study NCT ID:
NCT00873678
Status:
COMPLETED
Last Update Posted:
2010-06-03
First Post:
2009-03-31
Brief Title:
Assessment of the Prevalence of Genes AHI1 NPHP1 and CEP290 in Joubert Syndrome
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Assessment of the Prevalence and Mutational Spectrum of Genes AHI1 NPHP1 and CEP290 in Joubert Syndrome and Cerebello-oculo-renal Syndromes
Status:
COMPLETED
Status Verified Date:
2010-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
JSCORS
Brief Summary:
Primary objective
assessment of the prevalence of AHI1 mutations in Joubert syndrome and cerebello-oculo-renal syndromes JSCORS
Secondary objective
assessment of the prevalence of CEP290 mutations and NPHP1 homozygous deletions in JSCORS
caracterization of mutational spectrum of AHI1 NPHP1 CEP290 genes in JSCORS
evaluation of genotype-phenotype correlation in JSCORS
assessment of the prevalence of AHI1 mutations in Joubert syndrome and cerebello-oculo-renal syndromes JSCORS
Secondary objective
assessment of the prevalence of CEP290 mutations and NPHP1 homozygous deletions in JSCORS
caracterization of mutational spectrum of AHI1 NPHP1 CEP290 genes in JSCORS
evaluation of genotype-phenotype correlation in JSCORS
Detailed Description:
Design multicentric Aims of this study to describe clinical and genetic basis of Joubert syndrome and cerebello-oculo-renal syndromesJoubert syndrome JS is characterized by hypotonia abnormal ocular movements and neonatal breathing dysregulation evolving into developmental delay ataxia oculomotor apraxia with variable mental retardation The neuroradiological hallmark of JS is a complex midbrain-hindbrain malformation consisting of vermis hypoplasiadysplasia a deepened interpeduncular fossa and thickened elongated and mal-orientated superior cerebellar peduncles Molar Tooth Sign MTS Other organs could be involved in JS kidneys nephronophthisis or cystic dysplastic kidneys eyes Leber Congenital Amaurosis retinopathy colobomas liver hepatic fibrosis others polydactyly tongue hamartomas situs inversus Several associated central nervous system malformations were described polymicrogyria hydrocephalus corpus callosum anomalies and encephalocele This pleiotropic involvement identifies a large spectrum of cerebello-oculo-renal syndromes or JS Related Disorders JSRD
Joubert syndrome and cerebello-oculo-renal syndromes JSCORS are autosomal recessive conditions associated with a high risk of recurrence for further pregnancies 25 In 2004 mutations in AHI1 gene Abelson helper integration site gene were identified in 7-11 JS but the disease is caracterized by a wide genetic heterogeneity At least five others genes are involved in JSCORS NPHP1 which homozygous deletions are responsible for a small percentage of JS 2 and more recently CEP290 gene which exact mutations prevalence remained to be evaluated
Using molecular analysis of those three genes sequencing of 29 coding exons of AHI1 and 54 exons of CEP290 searching for NPHP1 homozygous deletions by PCR analysis we project to study respective prevalence of mutations of those three genes and described associated phenotypes in 65 JSCORS patients This work will allowed to described genotype-phenotypes correlation in JSCORS and to progress in the characterization of the underlying pathogenetic mechanisms It will be the first step before identification of novel disease genes
Joubert syndrome and cerebello-oculo-renal syndromes JSCORS are autosomal recessive conditions associated with a high risk of recurrence for further pregnancies 25 In 2004 mutations in AHI1 gene Abelson helper integration site gene were identified in 7-11 JS but the disease is caracterized by a wide genetic heterogeneity At least five others genes are involved in JSCORS NPHP1 which homozygous deletions are responsible for a small percentage of JS 2 and more recently CEP290 gene which exact mutations prevalence remained to be evaluated
Using molecular analysis of those three genes sequencing of 29 coding exons of AHI1 and 54 exons of CEP290 searching for NPHP1 homozygous deletions by PCR analysis we project to study respective prevalence of mutations of those three genes and described associated phenotypes in 65 JSCORS patients This work will allowed to described genotype-phenotypes correlation in JSCORS and to progress in the characterization of the underlying pathogenetic mechanisms It will be the first step before identification of novel disease genes
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None