Table 2

Seven different MKS3/TMEM67 mutations in four families with Joubert/COACH syndrome

FamilyEthnic originNucleotide change*Deduced protein change*Exon (allele)Parental consanguinityKidney (age at ESRF in years)EyeLiverBrain
F190Germanyc.755T→Cp.M252T8, 18 (compound heterozygous)NoNPHP (14)Nystagmus, oculomotor apraxia chorioretinal colobomaLiver fibrosisAtaxia, PR
F56Germanyc.130C→Tp.Q44X1, 24 (compound heterozygous)NoNPHP (12)Retinal degeneration, chorioretinal coloboma,NDAtaxia, CVH
A144Germanyc.622A→Tp.R208X6, 24 (compound heterozygous)NoNPHP (15)NADLiver fibrosisMental retardation, CVA
A1371-II1, A1371-II2Moroccoc.1888T→Cp.S630P19 (homozygous)YesNPHP (8)Blindness, strabism, ptosis, retinal colobomaLiver fibrosisAtaxia, hypotonia, PR, CVA
NPHP (<10)BlindnessLiver fibrosisauditory problems, CVA
  • COACH, Cerebellar vermis hypo/aplasia, Oligophrenia, congenital Ataxia, Coloboma and congenital Hepatic fibrosis; CVA, cerebellar vermis aplasia; CVH, cerebellar vermis hypoplasia; ESRF, end stage renal failure; NAD, nothing abnormal detected; NPHP, nephronophthisis; PR, psychomotor retardation.

  • *Mutation numbering is based on MKS3/TMEM67 human reference sequence NM_153704.5, where +1 corresponds to the A of ATG start translation codon.

  • Novel mutations are highlighted in bold. All mutations were absent from at least 91 healthy control subjects.