Table 1 Summary of clinical features for JS subjects with AHI1 and NPHP1 mutations*.
| Pedi‐ gree | Ethnicity | Sequence change† | Protein change‡/ effect | Con‐ sang | Age§ | Sex | CNS¶ | Eye move‐ ments | Ret‐ ina | Respir‐ atory | Renal | Other** | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| New AHI1 mutations | |||||||||||||
| K8062 | Caucasian | Ex 6: 517 A>T | K246X | No | 18 | F | MTS | OMA, | RD | – | Left | DM | |
| Ex 18: 1995 T>G | L832X | nys | MCDK | ||||||||||
| K8090 | Caucasian | Ex 6: 662 C>G | S221X | No | 4 | M | MTS | – | RD | Tachy | – | – | |
| Ex 13: 1898 ins GG | fsX648 | ||||||||||||
| K8067 | Caucasian | IVS8 (−2 A>G) | Presumed | No | 6 | F | MTS | OMA, | RD | Apnea | – | – | |
| splice error | nys | ||||||||||||
| Ex 9: 1260 G>A | W420X | ||||||||||||
| K8019†† | Caucasian | Ex 9: 1267 C>T | Q423X | Yes | 5 | F | MTS‡‡ | NA | “Poor | Tachy | – | – | |
| homozygous | vision” | ||||||||||||
| K8052†† | Armenian | Ex 9: 1267 C>T | Q423X | Yes | 21 | M | MTS | Nys | RD | Tachy | – | – | |
| homozygous | |||||||||||||
| K8075 | Caucasian | Ex 9: 1267 C>T | Q423X | No | 5 | M | MTS | OMA, nys | RD | Tachy | – | – | |
| Ex 15: 2212 C>T | R738X | ||||||||||||
| K8107 | Turkish | IVS11 (+5 ins | Presumed | Yes | 26/9 | M/F | NA/MTS | NA/NA | RD/− | +/NA | Cysts/− | −/− | |
| TTAC) homozygous | splice error | ||||||||||||
| K8012†† | Icelandic | IVS14 (+1 G>T) | Presumed | Yes | 30/26 | F/M | MTS/MTS | Nys/nys | RD/RD | Tachy/ | NPH/ | −/− | |
| homozygous | splice error | tachy | NPH, | ||||||||||
| cysts | |||||||||||||
| K8103†† | Saudi | Ex 15: 2156 A>G | D719G | Yes | 4/3 | M/M | MTS/MTS | Nys/nys | RD/NA | Tachy/− | Left hydro‐ | −/− | |
| Arabian | homozygous | neph/− | |||||||||||
| K8018 | Caucasian | Ex 15: 2452 T>C | W725R | No | 10 | F | MTS | OMA, nys | RD | – | – | – | |
| Unknown | Unknown | ||||||||||||
| K8127 | Turkish | Ex 14: 1917 T>A | Y639X | Yes | 4 | F | MTS | Nys | RD | Tachy | – | – | |
| homozygous | |||||||||||||
| K8131 | Turkish | Ex 14: 2012 C>T | T671I | Yes | 8 | F | MTS | Nys | RD | NA | – | – | |
| homozygous | |||||||||||||
| K8134 | Turkish | Ex 19: 2687 A>G | H896R | Yes | 9/2 | F/M | MTS/MTS | Nys/nys | −/− | −/− | −/− | −/− | |
| homozygous | |||||||||||||
| Totals | 8/13 | 2–30 years | 9F/8M | 12/13 | 9/10 | 11/12 | 8/12 | 3/13 | 0/13 | ||||
| Published AHI1 mutations | |||||||||||||
| MTI‐01010 | Palestinian | Ex 7: 787 ins C | fsX270 | Yes | 1 aff child | M | MTS | OMA | NA | + | – | – | |
| homozygous | |||||||||||||
| MTI‐11510 | Kuwaiti | Ex 9: 1188‐9 del TG | fsX408 | Yes | 2 aff | M/F | MTS, PMG, | OMA | RD/RD | – | – | – | |
| homozygous | thin CC | ||||||||||||
| MTI‐14410 | Turkish | Ex 9: 1328 T>A | V443D | Yes | 1 aff | F | MTS, PMG, | OMA | NA | + | NA | ASD | |
| homozygous | thin CC | ||||||||||||
| Pedigree 39 | Saudi | Ex 9: 1328 T>A | V443D | Yes | 1 aff | M | MTS | NA | NA | NA | NA | – | |
| Arabian | homozygous | child | |||||||||||
| Pedigree 19 | Saudi | Ex 8: 1051 C>T | R351X | Yes | 3 aff | 3M | MTS | OMA, | NA | NA | NA | Mirror | |
| Arabian | homozygous | children | nys | mvts | |||||||||
| Pedigree 29 | Saudi | Ex 9: 1303 C>T | R435X | Yes | 2 | M/M | MTS | OMA | NA | NA | NA | Mirror | |
| Arabian | homozygous | children | or nys | mvts | |||||||||
| Family 129 | Turkish | Not identified | Not | Yes | 5 aff | 3F/2M | MTS | Nys in 1 | RD in 1 | NA | – | GR, | |
| identified | children | scoli‐ | |||||||||||
| (17–28) | osis, sz | ||||||||||||
| Family 229 | Swiss | Not identified | Not | Yes | 2 aff | F/F | MTS | Nys in 1 | RD in 1 | + | – | – | |
| identified | children | ||||||||||||
| (2, 23) | |||||||||||||
| Published NPHP1 mutations | |||||||||||||
| K807611 | Caucasian | Homozygous | No protein | No | 12/8 | F/F | MTS§§/NA | OMA/ | −/− | −/− | NPH/− | −/− | |
| deletion | made | OMA | |||||||||||
| K808411 | Caucasian | Homozygous | No protein | No | 17 | M | MTS§§ | – | – | – | NPH | – | |
| deletion | made | ||||||||||||
| Patient EC12 | Italian | Homozygous | No protein | No | 3 | F | MTS§§ | OMA | RD | – | NPH | – | |
| deletion | made | ||||||||||||
*+, present; −, absent; ASD, atrial septal defect; CC, corpus callosum; CNS, central nervous system involvement; Consang, consanguinity; DM, diabetes mellitus; Ex, exon; F, female; GR, growth retardation; hydroneph, hydronephrosis; IVS, intron; M, male; MCDK, multicystic dysplastic kidney; Mirror mvts, mirror movements; MTS, molar tooth sign on MRI; OMA, oculomotor apraxia; NA, information not available; NPH, nephronophthisis; Nys, nystagmus; PMG, polymicrogyria; RD, retinal dystrophy; sz, seizures; Tachy, tachypnea
†DNA mRNA sequences are numbered starting from the A of the ATG initiator codon (nucleotide +1); exons (Ex) are numbered by convention of the Ensembl assembly for GenBank accession number AJ459824.
‡Proteins are numbered starting from the initiator methionine codon 1.
§Age in years when last ascertained; aff, affected.
¶Note that all subjects had hypotonia, ataxia, and mental retardation or developmental delay, which was milder in those with NPHP1 deletions.
**Other includes polydactyly, hepatic fibrosis, occipital encephaloceles, and ocular coloboma.
††Family compatible with linkage to 6q23 by haplotype analysis.
‡‡Unable to confirm MTS but early studies showed cerebellar vermis hypoplasia prior to description of MTS.
§§Molar tooth has distinctive appearance with elongated but not thickened superior cerebellar peduncles.