Disease relevance of JBTS1

• Joubert syndrome (JS) is an autosomal recessive developmental brain condition characterized by hypoplasia/dysplasia of the cerebellar vermis and by ataxia, hypotonia, oculomotor apraxia, and neonatal breathing dysregulation [1].
• A form of JS that includes retinal dysplasia and cystic dysplastic kidneys has been differentiated from other forms of JS, called either "JS type B" or "cerebello-oculo-renal syndrome" (CORS), but the genetic basis of this condition is unknown [1].
• BACKGROUND: Joubert syndrome (JS) is a recessively inherited disorder characterised by hypotonia at birth and developmental delay, followed by truncal ataxia and cognitive impairment, characteristic neuroimaging findings (cerebellar vermis hypoplasia, "molar tooth sign") and suggestive facial features [2].
• JS is clinically heterogeneous with some patients presenting with breathing abnormalities in the neonatal period, oculomotor apraxia, retinal dystrophy, retinal coloboma, ptosis, hexadactyly, and nephronophtisis or cystic dysplastic kidneys [2].
• The molecular basis of nephronophthisis, the most frequent genetic cause of renal failure in children and young adults, and its association with retinal degeneration and cerebellar vermis aplasia in Joubert syndrome are poorly understood [3].

Psychiatry related information on JBTS1

• Joubert syndrome (JS) is an autosomal recessive multisystem disease characterized by cerebellar vermis hypoplasia with prominent superior cerebellar peduncles (the "molar tooth sign" [MTS] on axial magnetic resonance imaging), mental retardation, hypotonia, irregular breathing pattern, and eye-movement abnormalities [4].
• Although both children showed developmental disabilities, the degree of cognitive delay was significantly less than that described in previous reports of children with Joubert syndrome [5].
• The symptoms in this patient are different from those in the Joubert syndrome, Rett syndrome, Rett-like variants, and of a case reported by Leifer et al [6].
• This study describes the relationship between parenting stress and behavior in children with Joubert syndrome, a rare genetic neurodevelopmental disorder [7].
• Findings provide a better understanding of the impact of child behavior on parents caring for a child with Joubert syndrome [7].

High impact information on JBTS1

• Abrogation of its function in zebrafish recapitulates the renal, retinal and cerebellar phenotypes of Joubert syndrome [3].
• Joubert syndrome is a congenital brain malformation of the cerebellar vermis and brainstem with abnormalities of axonal decussation (crossing in the brain) affecting the corticospinal tract and superior cerebellar peduncles [8].
• Joubert syndrome (JS) is an autosomal recessive disorder characterized by cerebellar vermis hypoplasia associated with hypotonia, developmental delay, abnormal respiratory patterns, and abnormal eye movements [9].
• Occipital encephalocele and/or polydactyly have occasionally been reported in some patients with JS, and these phenotypic features can also be observed in Meckel-Gruber syndrome (MKS) [9].
• The NPHP1 gene deletion associated with juvenile nephronophthisis is present in a subset of individuals with Joubert syndrome [4].

Chemical compound and disease context of JBTS1

• We review the anesthetic implications of Joubert syndrome and report that spinal anesthesia under intravenous propofol sedation proved satisfactory for repair of an inguinal hernia in a spontaneously ventilating infant with this syndrome [10].

Biological context of JBTS1

• Here, we describe a large consanguineous family with JS and nephronophthisis, representing a novel cerebello-renal phenotype [11].
• We conclude that Joubert syndrome is clinically and genetically heterogeneous and that one locus maps to chromosome 9q [12].
• 7. The second family did not show linkage to this region, giving a first indication of genetic heterogeneity underlying Joubert syndrome [12].
• Here, we identify two frameshift mutations and one missense mutation in the AHI1 gene in three consanguineous families with JS, some with cortical polymicrogyria [13].
• Analysis of an additional 21 unrelated JS patients showed no evidence of homozygosity at the 9q34 and 17p11.2 loci that would suggest inheritance of founder JS mutation(s) or unreported consanguinity [14].

Anatomical context of JBTS1

• We find that JBTS1 and -3 primarily show features restricted to the central nervous system, with JBTS1 showing largely pure cerebellar and midbrain-hindbrain junction involvement, and JBTS3 displaying cerebellar, midbrain-hindbrain junction, and cerebral cortical features, most notably polymicrogyria [15].
• We describe several disorders in addition to Joubert syndrome with the distinctive radiologic sign known as the "molar tooth sign," comprised of midbrain and hindbrain malformations [16].
• Careful search for the subtle facial changes characteristic of this disorder as well as coloboma, cleft palate/bifid uvula, short neck, syndactyly, and hypoplasia of the nails is warranted when evaluating children with Dandy-Walker malformation with or without clinical signs of Joubert syndrome [17].
• Brain stem and cerebellar findings in Joubert syndrome [18].
• These results indicate that Joubert syndrome results from maldevelopment of the midbrain and cerebellar vermis, producing a pathognomonic sign on MRI [19].

Associations of JBTS1 with chemical compounds

• Here, we describe a child with Joubert syndrome presenting with primary lactic acidemia, decreased pyruvate oxidation rates, decreased ATP production, and a mildly decreased pyruvate dehydrogenase complex activity measured in a fresh muscle biopsy [20].
• The role of 99mTc DMSA renal scintigraphy in Joubert syndrome [21].

Other interactions of JBTS1

• JS is also genetically heterogeneous, with two known loci, on 9q34 (JBTS1) and 11p11-q12 (CORS2), representing only a fraction of cases [2].
• Furthermore, the mapping assignment and the expression pattern make BARHL1 an attractive positional candidate gene for a form of Joubert syndrome, a rare developmental anomaly of the cerebellum in humans [22].
• A search for mutations in WNT1 in a series of patients with Joubert syndrome did not detect mutations at this locus [23].
• Joubert syndrome: a haplotype segregation strategy and exclusion of the zinc finger protein of cerebellum 1 (ZIC1) gene [24].
• Over three decades have passed since Marie Joubert described the original proband for Joubert syndrome, a rare neurological disorder featuring absence of the cerebellar vermis (i.e. midline) [25].

Analytical, diagnostic and therapeutic context of JBTS1

• Prenatal diagnosis for Joubert syndrome [26]?
• We sought to explore the cerebral and cerebellar activation pattern elicited by finger tapping in an adolescent with Joubert syndrome and in a normal control subject using functional MRI [27].
• Joubert syndrome: early diagnosis by recognition of the behavioral phenotype and confirmation by cranial sonography [28].
• Scintigraphy may have a great value in the diagnosis and evaluation of the presence and severity of renal involvement in Joubert syndrome since it can evaluate kidney parenchyma and functioning renal tissue [21].
• Here we report 2 patients with Joubert syndrome in whom renal involvement was demonstrated by ultrasonography as renal cystic disorders which represented nephronophtisis [21].

References