Assessment of the Prevalence of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome (JSCORS)


Assistance Publique - Hôpitaux de Paris




Joubert Syndrome
Cerebello-oculo-renal Syndromes


Biological: Whole blood sample

Study type


Funder types




Details and patient eligibility


Primary objective: * assessment of the prevalence of AHI1 mutations in Joubert syndrome and cerebello-oculo-renal syndromes (JS/CORS) Secondary objective: * assessment of the prevalence of CEP290 mutations and NPHP1 homozygous deletions in JS/CORS * caracterization of mutational spectrum of AHI1, NPHP1, CEP290 genes in JS/CORS. * evaluation of genotype-phenotype correlation in JS/CORS.

Full description

Design: multicentric Aims of this study: to describe clinical and genetic basis of Joubert syndrome and cerebello-oculo-renal syndromes.Joubert 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 hypoplasia/dysplasia, 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 (JS/CORS) 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 JS/CORS : 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.


80 patients




No Healthy Volunteers

Inclusion criteria

  • Child or adult patients without age maximum

  • Affected with JS/CORS défined by neurologic disease with at least one of the following symptoms :

    • neonatal hypotonia or developmental delay (before age 3) or mental retardation (QD<70) (after age 3).
    • Ataxia
    • Oculomotor apraxia
  • and on MRI :

    • vermis hypoplasia/agenesia defined by insufficient development of cerebellar vermis.
    • And molar tooth defined by thickened, elongated and mal-orientated superior cerebellar peduncles on axial sections.

Exclusion criteria

  • Chromosomal anomalies identified by caryotype
  • Absence of signature of informed consent.
  • Absence of affiliation to social security

Trial design

80 participants in 1 patient group

Children or adult patients affected with JS/CORS
Biological: Whole blood sample

Trial contacts and locations



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