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** | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| *+, 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. | |||||||||||||
| 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 | ||||||||||||