Joubert-like syndrome unlinked to known candidate loci

Janecke, Andreas R.; Müller, Thomas; Gaßner, Ingmar; Kreczy, Alfons; Schmid, E. D.; Kronenberg, Florian; Utermann, Barbara; Utermann, Gerd

doi:10.1016/j.jpeds.2003.11.010

Cited by 20 publications

(11 citation statements)

References 21 publications

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“…The Malta family did not show linkage to the CORS2 (JBTS2) locus or any of the MKS loci [Valente et al, 2005]. A consanguineous Austrian family with two affected cousins and a fetus was reported with a JSRD characterized by optic colobomas, morning glory disc anomaly, and cystic dysplastic kidneys [Janecke et al, 2004]. Linkage to JBTS1 was excluded.…”

Section: Discussionmentioning

confidence: 99%

Meckel syndrome in the Hutterite population is actually a Joubert‐related cerebello‐oculo‐renal syndrome

Boycott

Parboosingh

Scott³

et al. 2007

American J of Med Genetics Pt A

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Meckel syndrome (MKS) is a rare lethal autosomal recessive disorder characterized by the presence of occipital encephalocele, cystic kidneys, fibrotic changes of the liver and polydactyly. Joubert syndrome (JS)-related disorders (JSRDs) or cerebello-oculo-renal syndromes (CORS) are a group of recessively inherited conditions characterized by a molar tooth sign (MTS) on cranial MRI, a set of core clinical features (developmental delay/mental retardation, hypotonia, ataxia, episodic breathing abnormalities, abnormal eye movements) and variable involvement of other systems including renal, ocular, central nervous system, craniofacial, hepatic, and skeletal. A significant clinical overlap between MKS and JSRD/CORS has been recognized in the literature. We describe a group of 10 Hutterite patients, of which 7 had been previously diagnosed with MKS, with a JSRD. Clinical features include variable early mortality, cognitive handicap, a characteristic dysmorphic facial appearance, hypotonia, ataxia, abnormal breathing pattern, nystagmus, and MTS on MRI. Additional features include occipital encephalocele, posterior fossa fluid collections resembling Dandy-Walker malformation, hydrocephalus, coloboma, and renal disease. This JSRD is a recognizable dysmorphic syndrome characterized by hypertelorism, deep-set eyes, down-slanting palpebral fissures, ptosis, arched eyebrows with medial sparseness, square nasal tip, short philtrum with tented upper lip, open mouth with down-turned corners, and posteriorly rotated low-set ears. Renal disease is present in 70% of patients and is characterized by cystic kidneys, abnormalities in renal function and hypertension. Homozygous deletions of NPHP1 and the known loci for JS/JSRD and MKS were excluded by identity-by-descent mapping studies suggesting that this condition in the Hutterites represents yet another locus for a JSRD.

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Section: Discussionmentioning

confidence: 99%

Meckel syndrome in the Hutterite population is actually a Joubert‐related cerebello‐oculo‐renal syndrome

Boycott

Parboosingh

Scott³

et al. 2007

American J of Med Genetics Pt A

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“…It is important to remember that testing guidelines will continue to evolve as knowledge increases and that many manifestations are age‐dependent and may not be present in infants or young children. In addition, the etiology will remain elusive in up to half of all patients, as additional JSRD genes remain to be identified, as supported by the observation of consanguineous families that do not map to any of the known loci [Janecke et al, 2004; Valente et al, 2005; Boycott et al, 2007].…”

Section: Molecular Genetics Of Jsrdmentioning

confidence: 99%

Clinical and molecular features of Joubert syndrome and related disorders

Parisi

2009

American J of Med Genetics Pt C

223

239

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Joubert syndrome (JBTS; OMIM 213300) is a rare, autosomal recessive disorder characterized by a specific congenital malformation of the hindbrain and a broad spectrum of other phenotypic findings that is now known to be caused by defects in the structure and/or function of the primary cilium. The complex hindbrain malformation that is characteristic of JBTS can be identified on axial magnetic resonance imaging and is known as the molar tooth sign (MTS); other diagnostic criteria include intellectual disability, hypotonia, and often, abnormal respiratory pattern and/or abnormal eye movements. In addition, a broad spectrum of other anomalies characterize Joubert syndrome and related disorders (JSRD), and may include retinal dystrophy, ocular coloboma, oral frenulae and tongue tumors, polydactyly, cystic renal disease (including cystic dysplasia or juvenile nephronophthisis), and congenital hepatic fibrosis. The clinical course can be variable, but most children with this condition survive infancy to reach adulthood. At least 8 genes cause JSRD, with some genotype-phenotype correlations emerging, including the association between mutations in the MKS3 gene and hepatic fibrosis characteristic of the JSRD subtype known as COACH syndrome. Several of the causative genes for JSRD are implicated in other ciliary disorders, such as juvenile nephronophthisis and Meckel syndrome, illustrating the close association between these conditions and their overlapping clinical features that reflect a shared etiology involving the primary cilium.

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“… 52 In addition, a distinctive optic disc anomaly was reported in a large Austrian family. 53 Encephalocele, hydrocephalus and cystic kidney disease are common in JBTS14 phenotype. Furthermore, tmem237 knockdown in zebrafish caused gastrulation defects consistent with ciliary dysfunction, similar to defects resulting from knockdown of transition zone proteins, including Mks3 (TMEM67; MIM 609884 ) and Tmem216 (MIM 613277) .…”

Section: Molecular Aspects Of Js and Jsrds In Arab Familiesmentioning

confidence: 99%

Mutation spectrum of Joubert syndrome and related disorders among Arabs

et al. 2014

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Joubert syndrome (JS) is a rare autosomal recessive (AR), neurological condition characterized by dysgenesis of the cerebellar vermis with the radiological hallmark of molar tooth sign, oculomotor apraxia, recurrent hyperventilation and intellectual disability. Most cases display a broad spectrum of additional features, including polydactyly, retinal dystrophy and renal abnormalities, which define different subtypes of JS-related disorders (JSRDs). To date, 23 genes have been shown to cause JSRDs, and although most of the identified genes encode proteins involved in cilia function or assembly, the molecular mechanisms associated with ciliary signaling remain enigmatic. Arab populations are ethnically diverse with high levels of consanguinity (20-60%) and a high prevalence of AR disorders. In addition, isolated communities with very-high levels of inbreeding and founder mutations are common. In this article, we review the 70 families reported thus far with JS and JSRDs that have been studied at the molecular level from all the Arabic countries and compile the mutations found. We show that JS and the related JSRDs are genetically heterogeneous in Arabs, with 53 mutations in 15 genes. Thirteen of these mutations are potentially founder mutations for the region.

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Joubert-like syndrome unlinked to known candidate loci

Cited by 20 publications

References 21 publications

Meckel syndrome in the Hutterite population is actually a Joubert‐related cerebello‐oculo‐renal syndrome

Meckel syndrome in the Hutterite population is actually a Joubert‐related cerebello‐oculo‐renal syndrome

Clinical and molecular features of Joubert syndrome and related disorders

Mutation spectrum of Joubert syndrome and related disorders among Arabs

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