Four different MKS3/TMEM67 mutations in five families with nephronophthisis (NPHP) and associated liver fibrosis
| Family | Ethnic origin | Nucleotide change† | Deduced protein change† | Exon (mutation) | Parental consanguinity | Kidney (age at ESRF in years) | Eye | Liver | Other | Brain |
| A1011 | Germany | c.869 G→T | p.W290L | 8, 18 (compound heterozygous) | No | NPHP, Bx (8) | Strabismus, nystagmus | Liver fibrosis | – | Mild statomotoric retardation, no MRI |
| c.1843 T→C | p.C615R | |||||||||
| F585 | Turkey | c.1843 T→C | p.C615R | 18 (homozygous) | 1stdegree cousin | NPHP, Bx (6) | Retinal degeneration | Liver fibrosis | – | Mild cortical atrophy, normal cerebellum |
| F519 | Germany | c.1843 T→C | p.C615R | 18 (homozygous) | No | NPHP, Bx (6) | NAD | Liver fibrosis | Ehlers–Danlos syndrome | No neurological anomalies, no MRI |
| F563* | Turkey | c.2461 G→A | p.G821S | 24 (homozygous) | 4th degree cousin | NPHP (14) | Normal fundus | Liver fibrosis | – | No neurological anomalies, no MRI |
| NPHP Bx (10), | Normal fundus | Liver fibrosis | – | No neurological anomalies, normal MRI (fig 4) | ||||||
| NPHP (9) | Normal fundus | Liver fibrosis | – | No neurological anomalies, no MRI | ||||||
| F1039 | Germany | c.2461 G→C | p.G821R | 24 (homozygous) | No | NPHP (10) | Anisocoria | Liver fibrosis | – | Normal MRI, PR |
Bx, Kidney biopsy is compatible with the diagnosis of nephronophthisis; ESRF, end stage renal failure; MRI, magnetic resonance imaging; NAD, nothing abnormal detected; ND, no data; NPHP, nephronophthisis; PR, psychomotor retardation.
*Family has three affected siblings.
†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.