| Home | E-Submission | Sitemap | Contact Us
Child Kidney Dis > Volume 19(1); 2015 > Article
Kang and Cheong: Nephronophthisis

Abstract

NPHP is the most common monogenic cause of CKD in children or adolescents. Extra-renal symptoms often accompany, therefore examination of retina, hearing, and skeleton is necessary in patients with CKD with insidious onset. Genes involved in NPHP-RC are mostly related in primary cilia. While genetic diagnosis is necessary for definitive diagnosis, there is no curative treatment.

Nephronophthisis (NPHP), meaning ‘disappearance of nephrons’, is the most common monogenic cause of chronic renal failure (CRF) in children or adolescents [1-4]. For instance, among 160 end-stage renal disease (ESRD) patients of our center, one fourth had clinical diagnosis of NPHP.

Symptoms

NPHP typically has insidious onset, therefore when the diagnosis is made, most of the patients have advanced chronic kidney disease (CKD) with decreased renal function. Advanced CRF is accompanied by anemia and growth retardation, thus most of NPHP patients present with general weakness, pallor, and poor growth. History taking commonly reveals recent onset polyuria/nocturia and polydipsia, which is considered as resulting from decreased renal concentrating ability. Urinalysis is often normal [5], and the blood pressure is usually not high in early stage. Contrast to autosomal recessive or autosomal dominant polycystic kidney disease (ARPKD or ADPKD), kidney size of NPHP is usually normal or relatively small [6]. On ultrasonography, corticomedullary differentiation of the kidney is lost. Case 1 describes a typical case of juvenile NPHP.

1. Case 1

A 14 years old boy presented with both lower leg pain. He had suffered from general weakness, pallor, nocturia for some time. Laboratory test revealed anemia and azotemia. USG showed small kidneys with increased echogenicity and impaired perfusion (Fig. 1). He denied history of UTI, and his VCUG was normal.
NPHP is often accompanied by extra-renal symptoms, such as retinitis pigmentosa (RP) or Leber’s congenital amaurosis (LCA) in Senior-Løken syndrome (SLSN), hypo-/ a-plasia of cerebellar vermis in Joubert syndrome (JBTS), hepatic fibrosis in Meckel Gruber syndrome (MKS), and COACH (cerebellar vermis hypoplasia/ aplasia, oligophrenia, congenital ataxia, ocular coloboma, and hepatic fibrosis) syndrome with multiple problem [7], listing a few. Because most of the causative genes in these disorders encode proteins that play a role in the cilium [8-10], a collective term NPHP-related ciliopathy (NPHP-RC) is used to describe this group of diseases. Case 2 describes a case of COACH syndrome.

Case 2

A one year old girl presented with developmental delay and apraxia. Imaging studies revealed molar tooth sign' in brain stem (Fig. 2), multiple cysts in the kidneys and hepatic fibrosis. She lost her kidney function when she was 11 years old.

Diagnosis

Diagnostic criteria of NPHP are as follows [11].
Clinical diagnostic criteria of NPHP
Insidious onset of CRF the first thirty years, without identifiable cause.
Patients often presents with <30 years, idiopathic
Anemia, growth retardation
Polyuria, nocturia, polydipsia from Decreased concentrating ability of the kidneys.
Histological findings are non-specific showing chronic tubulointerstitial nephropathy (Fig. 3), therefore pathologic diagnosis is not mandatory for NPHP. Furthermore, since most of the patients present at their advanced stage, renal biopsy can be risky of bleeding complication. On electron microscopy, tubular basement membrane change is , similar to glomerular basement membrane change in Alport syndrome [12].
Since the clinical features of patients with NPHP-RC are rather non-specific, a genetic diagnosis is required for a definitive diagnosis of NPHP-RC. In addition, multiple syndromes of NPHP-RC share their phenotype in various degrees, which requires clarification of genetic aberration for appropriate diagnosis [10]. Inheritance pattern of NPHP-RC is commonly autosomal recessive (AR), and currently more than 20 causative genes of NPHP are known, with ‘NPHP’ as part of their names [13-15]. Table 1 shows list of genes searched with term ‘NPHP’, ‘SLSN’, ‘JBTS’, ‘MKS’ and ‘Bardet-Biedl syndrome (BBS, syndrome of NPHP, RP, obesity, polydactyly, cognitive impairment, and male infertility)’, representatives of NPHP-RC.
Among the known genes causing NPHP, a large deletion of NPHP1 is the most common, accounting for approximately one fifth of NPHP cases [16-20]. It is the first gene discovered as cause of NPHP, and it has homologous segments nearby, rendering this gene prone to large deletion (Fig. 4). Those with NPHP1 total deletion mostly have juvenile NPHP, whose onset of CRF is later than 5 years of age, with of ESRD about 13 yrs. Diagnosis of NPHP1 total deletion is rather straightforward, because multiplex PCR of NPHP1 exons does not produce band in NPHP1 total deletion. Recently, Korean patients with total NPHP1 deletion were reported to have unexpected findings of retinopathy with large or small flecks, compatible with Stargardt disease or albipunctatus retinopathy [21] (Fig. 5, 6); the authors suggested that children with impaired renal function of unknown cause should be screened for retinopathy, and retinopathy warrants screening for a homozygous deletion of NPHP1.
Other genes contribute less than 2-3% [9]. Some of them are strongly associated to certain phenotype, NPHP5 or NPHP6 mutation lead to RP, WDR19 (NPHP13) is associated with Caroli disease [22] (Fig. 7). On the other hand many of them share phenotypes, demonstrated by the number of genes associated with each syndrome (Table 1). Due to the large number of genes to test, recently. next-generation sequencing (NGS) is often applied, and about 1/3 patients obtain genetic diagnosis, implying that there are yet many genes to discover [23].

Pathogenesis

Primary cilia (Fig. 8) is present in almost all mammalian cells, functioning as sensory organelles, responding to flow, optic, osmotic, chemo or olfactory stimuli [24, 25], linking to various cellular function such as polarity, cell-cycle control [10]. Therefore defect of primary cilia of renal tubular cells results in cystic disease. Extra-renal symptoms are explained by presence of primary cilia in respective cells; Primary cilia at retina are photoreceptors, whose defect can cause retinopathy, oculomotor apraxia, nystagmus, and coloboma [10, 15, 26, 27]. Primary cilia in choangiocytes explain hepatic fibrosis in NPHP-RC [28]; Primary cilia in chondrocytes explains skeletal abnormalities such as short ribs, coneshaped epiphysis, and postaxial polydactyly in Jeune syndomre and JBTS or BBS [29, 30], especially with defect in genes of intra-flagella transport (IFT) [29].
Location, interacting molecules, and involved signaling pathway of respective causative genes are linked to the phenotype of various NPHP-RC. In addition, effect of additional mutations in another NPHP-RC genes or genetic modifiers has been suggested [9, 24, 31-33].

Treatment

There is no curative treatment for NPHP. Conservative management of CKD is necessary. There is no risk of recurrence after kidney transplantation; extra-renal symptoms progress irrespective of kidney transplantation.

Summary

NPHP is the most common monogenic cause of CKD in children or adolescents. Extra-renal symptoms often accompany, therefore examination of retina, hearing, and skeleton is necessary in patients with CKD with insidious onset. Genes involved in NPHP-RC are mostly related in primary cilia. While genetic diagnosis is necessary for definitive diagnosis, there is no curative treatment.

Acknowledgement

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number : HI1 2C0014).”

References

1. Helin I, Winberg J. Chronic renal failure in Swedish children. Acta Paediatr Scand. 1980 Sep. 69(5):607-11; PubMed PMID: 7234380. Epub 1980/09/01. eng.
crossref pmid
2. Steele BT, Lirenman DS, Beattie CW. Nephronophthisis. Am J Med. 1980 Apr. 68(4):531-8; PubMed PMID: 736923. Epub 1980/04/01. eng.
crossref pmid
3. Pistor K, Scharer K, Olbing H, Tamminen-Mobius T. Children with chronic renal failure in the Federal Republic of Germany: II. Primary renal diseases, age and intervals from early renal failure to renal death. Arbeitsgemeinschaft fur Padiatrische Nephrologie. Clin Nephrol. 1985 Jun. 23(6):278-84; PubMed PMID: 4028524. Epub 1985/06/01. eng.
pmid
4. Cantani A, Bamonte G, Ceccoli D, Biribicchi G, Farinella F. Familial juvenile nephronophthisis. A review and differential diagnosis. Clin Pediatr (Phila). 1986 Feb. 25(2):90-5; PubMed PMID: 351079. Epub 1986/02/01. eng.
crossref pmid
5. Hirano D, Fujinaga S, Ohtomo Y, Nishizaki N, Hara S, Murakami H, et al. Nephronophthisis Cannot Be Detected by Urinary Screening Program. Clin Pediatr (Phila). 2012 Apr 20. 52(8):759-61; PubMed PMID: 22523277. Epub 2012/04/24. Eng.
crossref pmid
6. Blowey DL, Querfeld U, Geary D, Warady BA, Alon U. Ultrasound findings in juvenile nephronophthisis. Pediatr Nephrol. 1996 Feb. 10(1):22-4; PubMed PMID: 8611349. Epub 1996/02/01. eng.
crossref pmid
7. Gentile M, Di Carlo A, Susca F, Gambotto A, Caruso ML, Panella C, et al. COACH syndrome: report of two brothers with congenital hepatic fibrosis, cerebellar vermis hypoplasia, oligophrenia, ataxia, and mental retardation. Am J Med Genet. 1996 Aug 23. 64(3):514-20; PubMed PMID: 8862632.
crossref pmid
8. Hildebrandt F, Otto E. Cilia and centrosomes: a unifying pathogenic concept for cystic kidney disease? Nature reviews Genetics. 2005 Dec. 6(12):928-40; PubMed PMID: 16341073. Epub 2005/12/13. eng.
crossref pmid
9. Chaki M, Hoefele J, Allen SJ, Ramaswami G, Janssen S, Bergmann C, et al. Genotype-phenotype correlation in 440 patients with NPHP-related ciliopathies. Kidney Int. 2011 Dec. 80(11):1239-45; PubMed PMID: 21866095. Epub 2011/08/26. eng.
crossref pmid pmc
10. Hildebrandt F, Attanasio M, Otto E. Nephronophthisis: disease mechanisms of a ciliopathy. J Am Soc Nephrol. 2009 Jan. 20(1):23-35; PubMed PMID: 19118152. Pubmed Central PMCID: 2807379. Epub 2009/01/02. eng.
crossref pmid pmc
11. Hildebrandt F, Strahm B, Nothwang HG, Gretz N, Schnieders B, Singh-Sawhney I, et al. Molecular genetic identification of families with juvenile nephronophthisis type 1: rate of progression to renal failure. APN Study Group. Arbeitsgemeinschaft fur Padiatrische Nephrologie. Kidney Int. 1997 Jan. 51(1):261-9; PubMed PMID: 8995741. Epub 1997/01/01. eng.
crossref pmid
12. Bollee G, Fakhouri F, Karras A, Noel LH, Salomon R, Servais A, et al. Nephronophthisis related to homozygous NPHP1 gene deletion as a cause of chronic renal failure in adults. Nephrol Dial Transplant. 2006 Sep. 21(9):2660-3; PubMed PMID: 16782989. Epub 2006/06/20. eng.
crossref pmid
13. Sang L, Miller JJ, Corbit KC, Giles RH, Brauer MJ, Otto EA, et al. Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell. 2011 May 13. 145(4):513-28; PubMed PMID: 21565611. Pubmed Central PMCID: 3383065. Epub 2011/05/14. eng.
crossref pmid pmc
14. Otto EA, Hurd TW, Airik R, Chaki M, Zhou W, Stoetzel C, et al. Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy. Nat Genet. 2010 Oct. 42(10):840-50; PubMed PMID: 20835237. Pubmed Central PMCID: 294 7620. Epub 2010/09/14. eng.
crossref pmid pmc
15. Wolf MT. Nephronophthisis and related syndromes. Curr Opin Pediatr. 2015 Apr. 27(2):201-11; PubMed PMID: 25635582.
crossref pmid
16. Nothwang HG, Stubanus M, Adolphs J, Hanusch H, Vossmerbaumer U, Denich D, et al. Construction of a gene map of the nephronophthisis type 1 (NPHP1) region on human chromosome 2q12-q13. Genomics. 1998 Jan 15. 47(2):276-85; PubMed PMID: 9479500. Epub 1998/02/28. eng.
crossref pmid
17. Hildebrandt F, Otto E, Rensing C, Nothwang HG, Vollmer M, Adolphs J, et al. A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1. Nat Genet. 1997 Oct. 17(2):149-53; PubMed PMID: 9326933. Epub 1997/11/05. eng.
crossref pmid
18. Soliman NA, Hildebrandt F, Otto EA, Nabhan MM, Allen SJ, Badr AM, et al. Clinical characterization and NPHP1 mutations in nephronophthisis and associated ciliopathies: a single center experience. Saudi J Kidney Dis Transpl. 2012 Sep. 23(5):10901-8; PubMed PMID: 22982934. Epub 2012/09/18. eng.
crossref
19. Otto EA, Ramaswami G, Janssen S, Chaki M, Allen SJ, Zhou W, et al. Mutation analysis of 18 nephronophthisis associated ciliopathy disease genes using a DNA pooling and next generation sequencing strategy. J Med Genet. 2011 Feb. 48(2):105-16; PubMed PMID: 21068128. Epub 2010/11/12. eng.
crossref pmid pmc
20. Saunier S, Calado J, Benessy F, Silbermann F, Heilig R, Weissenbach J, et al. Characterization of the NPHP1 locus: mutational mechanism involved in deletions in familial juvenile nephronophthisis. Am J Hum Genet. 2000 Mar. 66(3):778-89; PubMed PMID: 10712 196. Pubmed Central PMCID: 1288163. Epub 2000/03/11. eng.
crossref pmid pmc
21. Kang HG, Ahn YH, Kim JH, Ha IS, Yu YS, Park YH, et al. Atypical retinopathy in patients with nephronophthisis type 1: an uncommon ophthalmological finding. Clin Experiment Ophthalmol. 2014 Nov 17. PubMed PMID: 25401970.
crossref
22. Lee JM, Ahn YH, Kang HG, Ha IS, Lee K, Moon KC, et al. Nephronophthisis 13: implications of its association with Caroli disease and altered intracellular localization of WDR19 in the kidney. Pediatr Nephrol. 2015 Mar 1. PubMed PMID: 25726036.
crossref
23. Halbritter J, Porath JD, Diaz KA, Braun DA, Kohl S, Chaki M, et al. Identification of 99 novel mutations in a worldwide cohort of 1,056 patients with a nephronophthisis-related ciliopathy. Hum Genet. 2013 Apr 5. PubMed PMID: 23559409.

24. Hildebrandt F, Benzing T, Katsanis N. Ciliopathies. N Engl J Med. 2011 Apr 21. PubMed PMID: 21506742. Epub 2011/04/22. eng.

25. Omran H. NPHP proteins: gatekeepers of the ciliary compartment. J Cell Biol. 2010 Sep 6. 190(5):715-7; PubMed PMID: 20819931. Pubmed Central PMCID: 2935579. Epub 2010/09/08. eng.
crossref pmid pmc
26. Adams NA, Awadein A, Toma HS. The retinal ciliopathies. Ophthalmic Genet. 2007 Sep. 28(3):113-25; PubMed PMID: 17896309. Epub 2007/09/27. eng.
crossref pmid
27. Estrada-Cuzcano A, Roepman R, Cremers FP, den Hollander AI, Mans DA. Non-syndromic retinal ciliopathies: translating gene discovery into therapy. Hum Mol Genet. 2012 Aug 21. PubMed PMID: 22843501. Epub 2012/07/31. Eng.
crossref
28. Otto EA, Tory K, Attanasio M, Zhou W, Chaki M, Paruchuri Y, et al. Hypomorphic mutations in meckelin (MKS3/TMEM67) cause nephronophthisis with liver fibrosis (NPHP11). J Med Genet. 2009 Oct. 46(10):663-70; PubMed PMID: 19508969. Epub 2009/06/11. eng.
crossref pmid
29. Halbritter J, Bizet AA, Schmidts M, Porath JD, Braun DA, Gee HY, et al. Defects in the IFT-B component IFT172 cause Jeune and Mainzer-Saldino syndromes in humans. Am J Hum Genet. 2013 Nov 7. 93(5):915-25; PubMed PMID: 24140113. Pubmed Central PMCID: 3824130.
crossref pmid pmc
30. Cevik S, Sanders AA, Van Wijk E, Boldt K, Clarke L, van Reeuwijk J, et al. Active transport and diffusion barriers restrict Joubert Syndrome-associated ARL13B/ARL-13 to an Inv-like ciliary membrane subdomain. PLoS Genet. 2013;9(12):e1003977. PubMed PMID: 24339792. Pubmed Central PMCID: 3854969.
crossref
31. Tory K, Lacoste T, Burglen L, Moriniere V, Boddaert N, Macher MA, et al. High NPHP1 and NPHP6 mutation rate in patients with Joubert syndrome and nephronophthisis: potential epistatic effect of NPHP6 and AHI1 mutations in patients with NPHP1 mutations. J Am Soc Nephrol. 2007 May. 18(5):1566-75; PubMed PMID: 17409309. Epub 2007/04/06. eng.
crossref pmid
32. Hoefele J, Wolf MT, O'Toole JF, Otto EA, Schultheiss U, Deschenes G, et al. Evidence of oligogenic inheritance in nephronophthisis. J Am Soc Nephrol. 2007 Oct. 18(10):2789-95; PubMed PMID: 17855640. Epub 2007/09/15. eng.
crossref pmid
33. Parisi MA, Doherty D, Eckert ML, Shaw DW, Ozyurek H, Aysun S, et al. AHI1 mutations cause both retinal dystrophy and renal cystic disease in Joubert syndrome. J Med Genet. 2006 Apr. 43(4):334-9; PubMed PMID: 16155189. Pubmed Central PMCID: 2563230. Epub 2005/09/13. eng.
crossref pmid pmc
34. Wolf MT, Hildebrandt F. Nephronophthisis. Pediatr Nephrol. 2011 Feb. 26(2):181-94; PubMed PMID: 20652329. Epub 2010/07/24. eng.
crossref pmid pmc

Fig. 1.
Ultrasonography of the kidney in Case 1 showing typical finding of NPHP. Kidney size of NPHP is usually normal or relatively small, and corticomedullary differentiation of the kidney is lost.
ckd-19-1-23f1.tif
Fig. 2.
Brain MRI of Case 2 showing ‘molar tooth’ sign.
ckd-19-1-23f2.tif
Fig. 3.
Kidney biopsy of a patient with NPHP, showing interstitial inflammatory fibrosis with tubular basement membranes thickening (A, PAS staining) and cystic tubular enlargement (B, Masson's trichrome staining). Reprint with permission [12].
ckd-19-1-23f3.tif
Fig. 4.
NPHP1 with nearby homologous segments, rendering this gene prone to large deletion. Courtesy from Dr. Hae Il Cheong.
ckd-19-1-23f4.tif
Fig. 5.
The results of amplification of the exons of NPHP1 by polymerase chain reaction, which revealed a failure of amplification (homozygous deletion) of all exons of NPHP1 in patients. (Lanes 1 and 11, control subjects; lanes 2, 3, 6, 9, and 10, patients with total deletion of NPHP1; lanes 4, 5, 7, and 8, family members of patients). Reprint with permission [21].
ckd-19-1-23f5.tif
Fig. 6.
A fundus photograph and fundus fluorescein angiograms of the eyes of two Korean patients with total deletion of NPHP1. Left) (a) The fundus photograph shows a normal disc and yellow flecks on the posterior pole in the right and (b) left eyes. (c) A fluorescein angiogram 22s after dye injection shows multiple hyperfluorescent lesions corresponding to the flecks on the fundus photograph of the right eye. (d) A fluorescein angiogram 3.5min after dye injection shows no definite hyperfluorescence and choroidal silence in the left eye.
Right) (a) The fundus photograph shows a normal disc, a yellow fleck at the parafovea, and retinal pigment epithelium (RPE) degeneration along the major arcades without involvement of the far peripheral retinal area in the right (b) and left eyes. (c) A fluorescein angiogram 2min after dye injection shows a bull's eye appearance in the right eye. Maculopathy is shown with a foveal decrease in fluorescence surrounded by a continuous ring of increased fluorescence. Discrete areas of RPE atrophy (transmission window defect) surrounding the fovea (d). Reprint with permission [21].
ckd-19-1-23f6.tif
Fig. 7.
Liver images of patients with WDR19 mutations. (A) Abdominal Doppler ultrasonography reveals variable dilatation of the intrahepatic bile ducts in patient III-1. Red or blue tubular structures indicate hepatic vessels. (B) Axial computed tomography image of patient IV-1 shows globular enlargement of the liver and dilatation of the intrahepatic bile ducts (arrows), which are consistent with Caroli syndrome. Reprint with permission [22].
ckd-19-1-23f7.tif
Fig. 8.
Subcellular localization of the NPHP molecules nephrocystins. Nephrocystins are detected in the primary cilia, basal bodies, the mitotic spindle, focal adhesions, and adherens junctions. Most nephrocystins are expressed in the primary cilium (PC, enlarged box), the basal body (BB), and centrosomes (Cen) in a cell cycle-dependent manner. NPHP1 is expressed in the transition zone (TZ), focal adhesion plaques (FAP), adherens junctions (AJ), and tight junctions (TJ). Arrows in the cilium show the directions of the anterograde and retrograde transport along the microtubule transport. The intraflagellar transport is mediated by kinesin 2, a heterotrimeric protein that is composed of two motor units (Kif3a and Kif3b) and one nonmotor unit (KAP3). Sensory cilia transfer external stimuli. Wnt and hedgehog (Shh) signaling interfere with planar cell polarity by affecting the orientation of the centrosomes and mitotic spindles. Reprint with permission [34].
ckd-19-1-23f8.tif
Table 1.
NPHP-RC Genes
Gene Description MIM NPHPs (ESRD Age) JBTS MKS SLSN BBS IFT LF Comment
NPHP1* nephronophthisis 1 607100 NPHP1 (13yr) JBTS4 SLSN1 Most common
INVS* inversin 243305 NPHP2 (<4yr) SLSN + Situs inversus
NPHP3* nephronophthisis 3 608002 NPHP3 MKS7 SLSN3 + Situs inversus
NPHP4* nephronophthisis 4 607215 NPHP4 (21yr) SLSN4 +
IQCB1 IQ motif containing B1 609237 NPHP5 (13yr) SLSN5 LCA 100%
CEP290 centrosomal protein 290kDa 610142 NPHP6 JBTS5 MKS4 SLSN6 BBS14 20% of LCA
GLIS2 GLIS family zinc finger 2 608539 NPHP7 LCA
RPGRIP1L* RPGRIP1-like 610937 NPHP8 JBTS7 MKS5
NEK8 NIMA-related kinase 8 609799 NPHP9
SDCCAG8 serologically defined colon cancer antigen 8 613524 NPHP10 SLSN7 BBS16 LCA 80%
TMEM67 transmembrane protein 67 609884 NPHP11 JBTS6 MKS3 BBS +
TTC21B* tetratricopeptide repeat domain 21B 612014 NPHP12 JBTS11 BBS IFT139 Jeune
WDR19 WD repeat domain 19 608151 NPHP13 SLSN BBS IFT144 Jeune
ZNF423 zinc finger protein 423 604557 NPHP14, PKD JBTS19 Situs inversus
CEP164 centrosomal protein 164kDa 614848 NPHP15 (8yr) JBTS RP +
ANKS6 ankyrin repeat and sterile a motif domain containing 6 615370 NPHP16, PKD + Situs inversus
IFT172 intraflagellar transport 172 607386 NPHP17 JBTS IFT172
CEP83 centrosomal protein 83kDa 615847 NPHP18 (3yr) +
DCDC2 doublecortin domain containing 2 605755 NPHP19
XPNPEP3 X-prolyl aminopeptidase 3, mitochondrial 613553 NPHP1L CMP, Seizure
SLC41A1 solute carrier family 41, member 1 610801 NPHP2L Bronchiectasis
INPP5E inositol polyphosphate-5-phosphatase, 72 kDa 613037 JBTS1
TMEM216 transmembrane protein 216 613277 JBTS2 MKS2
AHI1* Abelson helper integration site 1 608894 JBTS3
ARL13B ADP-ribosylation factor-like 13B 608922 JBTS8
CC2D2A coiled-coil & C2 domain containing 2A 612013 JBTS9 MKS6
OFD1 oral-facial-digital syndrome 1 300170 JBTS10
KIF7 kinesin family member 7 611254 JBTS12
TCTN1 tectonic family member 1 609863 JBTS13
TMEM237 transmembrane protein 237 614423 JBTS14
CEP41 centrosomal protein 41kDa 610523 JBTS15
TMEM138 transmembrane protein 138 614459 JBTS16
C5orf42 Chr.5 open reading frame 42 614 571 JBTS17
TCTN3 tectonic family member 3 613847 JBTS18
TMEM231 transmembrane protein 231 614949 JBTS20 MKS11
CSPP1 centrosome and spindle pole associated protein 1 611654 JBTS21
PDE6D phosphodiesterase 6D, cGMP-specific, rod, delta 602676 JBTS22
MKS1 Meckel syndrome, type 1 609883 MKS1 BBS13
TCTN2 tectonic family member 2 613846 MKS8
B9D1 B9 protein domain 1 27077 MKS9
B9D2 B9 protein domain 2 80776 MKS10
BBS1 Bardet-Biedl syndrome 1 209901 BBS1
BBS2 Bardet-Biedl syndrome 2 606151 BBS2
ARL6 ADP-ribosylation factor-like 6 608845 BBS3
BBS4* Bardet-Biedl syndrome 4 600374 BBS4
BBS5 Bardet-Biedl syndrome 5 603650 BBS5
MKKS McKusick-Kaufman syndrome 604896 BBS6
BBS7 Bardet-Biedl syndrome 7 607590 BBS7
TTC8 tetratricopeptide repeat domain 8 608132 BBS8
BBS9 Bardet-Biedl syndrome 9 607968 BBS9
BBS10 Bardet-Biedl syndrome 10 610148 BBS10
TRIM32 tripartite motif containing 32 602290 BBS11
BBS12 Bardet-Biedl syndrome 12 610683 BBS12
WDPCP WD repeat containing planar cell polarity effector 613580 BBS15 LZTFL1
BBIP1 BBSome interacting protein 1 613605 BBS18
IFT27 intraflagellar transport 27 615870 BBS19
CCDC28B coiled-coil domain containing 28B 610162 BBS
WDR35 WD repeat domain 35 613602 IFT121
IFT122 intraflagellar transport 122 606045 IFT122
IFT140 intraflagellar transport 140 IFT140
IFT43 intraflagellar transport 43 614068 IFT43

Abbreviations: MIM, Mendelian inheritance in Men. NPHP, nephronophthisis. ESRD, end stage renal disease. JBTS, Joubert syndrome. MKS, Meckel Gruber syndrome. SLSN, Senior-Løken syndrome. BBS, Bardet-Biedl syndrome. IFT, intraflagella transport. LCA, Leber’s congenital amaurosis. LF, liver fibrosis.

TOOLS
PDF Links  PDF Links
PubReader  PubReader
ePub Link  ePub Link
Full text via DOI  Full text via DOI
Download Citation  Download Citation
Supplement  Supplement
  E-Mail
  Print
Share:      
METRICS
1
Crossref
6,651
View
35
Download
Editorial Office
50 Yonsei-Ro, Seodaemun-Gu, Department of Pediatrics, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea
TEL : +82-2-2228-2050   FAX : +82-2-393-9118   E-mail : chikd.editor@gmail.com

Copyright© Korean Society of Pediatric Nephrology. All rights reserved.                powerd by m2community
About |  Browse Articles |  Current Issue |  For Authors and Reviewers