Noor et al. (2008) ascertained a highly consanguineous Pakistani family segregating autosomal recessive mild to moderate mental retardation and retinitis pigmentosa (RP), with 4 living affected individuals; an additional family member with mental retardation was determined to be ... Noor et al. (2008) ascertained a highly consanguineous Pakistani family segregating autosomal recessive mild to moderate mental retardation and retinitis pigmentosa (RP), with 4 living affected individuals; an additional family member with mental retardation was determined to be a 48,XXXX phenocopy. Height, weight, and occipitofrontal circumference were within the normal range in all affected individuals, and there was no facial dysmorphism. The 3 older patients all had retinitis pigmentosa, astigmatism, and nystagmus; the youngest, at age 3 years, did not have RP but did have astigmatism and nystagmus. RP was not present in other members of the family. The oldest affected individual also had early cataract. Gorden et al. (2008) reviewed the brain MRIs of the patients reported by Noor et al. (2008) and determined that they had findings consistent with Joubert syndrome. In an erratum, Noor et al. (2008) agreed. Gorden et al. (2008) reported 7 families with Joubert syndrome linked to chromosome 4p. The clinical features were variable, but common features included the molar tooth sign, cerebellar vermis hypoplasia, and abnormal eye movements. Two patients had retinal dystrophy and 2 had a history of encephalocele. One patient had abnormal renal ultrasound and hepatosplenomegaly, and another had renal disease. One additional patient was a 22-year-old woman with agenesis of the corpus callosum, hydrocephalus, cerebellar vermis hypoplasia, abnormal eye movements, coloboma, mild renal disease, and hepatic fibrosis requiring liver transplant at age 10 years. Gorden et al. (2008) noted that the features in this patient were reminiscent of COACH syndrome (216360), which in some cases may be a variant representing a transitional phenotype between Joubert syndrome and Meckel syndrome (249000).
Bachmann-Gagescu et al. (2012) identified biallelic pathogenic mutations in the CC2D2A gene in 20 patients from 17 unrelated families with Joubert syndrome. The patients were ascertained from a larger cohort of 209 families with the disorder, yielding a ... Bachmann-Gagescu et al. (2012) identified biallelic pathogenic mutations in the CC2D2A gene in 20 patients from 17 unrelated families with Joubert syndrome. The patients were ascertained from a larger cohort of 209 families with the disorder, yielding a prevalence of about 8% for those with CC2D2A mutations. Patients with CC2D2A-related Joubert syndrome were more likely to have ventriculomegaly and seizures compared to Joubert syndrome patients without CC2D2A mutations. Although mutation-specific genotype-phenotype correlations could not be identified, most Joubert syndrome patients had at least 1 missense mutation, compared to those with the more severe Meckel syndrome, which tends to be associated with nonsense mutations (see 612013.0002).
In affected members of a consanguineous Pakistani family with Joubert syndrome, Noor et al. (2008) identified homozygosity for a splice site mutation in the CC2D2A gene (612013.0001) that segregated with the phenotype. The mutation was not found in ... In affected members of a consanguineous Pakistani family with Joubert syndrome, Noor et al. (2008) identified homozygosity for a splice site mutation in the CC2D2A gene (612013.0001) that segregated with the phenotype. The mutation was not found in 460 Pakistani control chromosomes. Gorden et al. (2008) identified 7 different mutations in the CC2D2A gene (see, e.g., 612013.0003-612013.0006) in 6 (9%) of 70 families with clinical features consistent with Joubert syndrome. Lee et al. (2012) reported 2 patients with Joubert syndrome who had a heterozygous mutation in the CC2D2A gene, consistent with JBTS9 (see 612013.0007 and 612013.0009), and a heterozygous mutation in the CEP41 gene (see 612013.0005 and 612013.0006), consistent with JBTS15 (614464), indicating digenic inheritance.