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ARL13B
| 2 families; phenotype ranged from classic JS to JS w/occipital encephalocele & pigmentary retinopathy [Cantagrel et al 2008]; no deletions/duplications reported. |
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B9D1
| 2 families, both w/"pure" form of JS; pathogenic variants in this gene also cause MKS. No deletions/duplications reported [Romani et al 2014]. |
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B9D2
| 2 families, both w/polydactyly & 1 w/encephalocele, cleft palate, & tongue hamartomas; pathogenic variants in this gene also cause MKS. No deletions/duplications reported [Bachmann-Gagescu et al 2015a]. |
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C2CD3
| 2 families identified in 1 series, both w/cleft palate and/or oral frenulae suggestive of features of OFD. No deletions/duplications reported [Bachmann-Gagescu et al 2015a]. |
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CEP41
| 3 families w/8 individuals w/JS described w/pathogenic variants in CEP41, based on screening at least 725 individuals w/JS, many of whom had been excluded for pathogenic variants in known JS-related genes. Slightly more than 50% of affected persons have demonstrated unilateral or bilateral postaxial polydactyly. Only 2 individuals have evidence of retinal disease, 1 of whom had unilateral coloboma, unilateral kidney disease, & ambiguous genitalia & died at age 7 days. Within 1 family, all 5 affected males had micropenis & 2 had growth hormone deficiency. Only splice site variants have been identified; no deletions/duplications reported [Lee et al 2012a]. |
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CEP104
| 3 families, all w/"pure" form of JS; no deletions/duplications reported [Srour et al 2015]. |
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CEP120
| 4/491 individuals w/JS had missense, frameshift, nonsense, or splice variants in this gene; phenotypes ranged from "pure" JS to MKS, OFD, and JS-JATD; no large deletions/duplications reported [Shaheen et al 2015b, Roosing et al 2016a]. |
|
IFT172
| 1/440 individuals with JS had missense pathogenic variants in this gene [Bachmann-Gagescu et al 2015a]. 2/12 families w/missense and/or truncating pathogenic variants had overlapping features of JS & JS-JATD (one w/Mainzer-Saldino syndrome features as well) including retinal dystrophy, hepatic fibrosis, NPHP, & cerebellar vermis hypoplasia. No deletions/duplications reported [Halbritter et al 2013]. |
| KATNIP (KIAA0556) | Homozygous truncating pathogenic variants in this gene identified in 3 sibs of a consanguineous family; 2/3 had panhypopituitarism (the male had micropenis & the female had a hypoplastic pituitary on MRI) [Sanders et al 2015]. In another consanguineous family, 2 sibs w/classic JS features had homozygous truncating pathogenic variants; no deletions/duplications reported [Roosing et al 2016b]. |
|
KIF7
| 3/440 families had pathogenic variants in this gene [Bachmann-Gagescu et al 2015a]. Individuals often have OFD features, w/or w/o other CNS findings such as agenesis/hypoplasia of the corpus callosum, hydrocephalus, & macrocephaly [Dafinger et al 2011, Putoux et al 2011]. The combination of polydactyly & these CNS findings suggests acrocallosal and/or hydrolethalus syndromes [Putoux et al 2011]. Nonsense & frameshift pathogenic variants predominate; no deletions/duplications reported. |
|
OFD1
| X-linked; no deletions/duplications reported. Pathogenic variants in this gene identified in 4/440 families [Bachmann-Gagescu et al 2015a] & in 2/250 families (2/84 w/only males affected) [Coene et al 2009]. Features include encephalocele, hydrocephalus, macrocephaly, polymicrogyria, polydactyly, & retinal disease. 1 family also had renal cystic disease, hydrocephalus, macrocephaly, & polymicrogyria [Field et al 2012]. |
|
PDE6D
| In 1 consanguineous family w/3 sibs (w/a homozygous splice site variant), phenotype included renal hypoplasia, retinal dystrophy, microphthalmia, ocular coloboma, & postaxial polydactyly [Thomas et al 2014]. |
|
POC1B
| A homozygous pathogenic missense variant in this gene was identified in an extended Iraqi family with LCA, enlarged, polycystic kidneys (resembling ADPKD rather than NPHP), & classic features of JS w/o liver fibrosis. Of note, the same homozygous pathogenic variant was identified in a family w/severe & slowly progressive cone-rod dystrophy w/o features of JS [Beck et al 2014]. No deletions/duplications reported. |
|
TCTN1
| 1/440 families had pathogenic variants in this gene [Bachmann-Gagescu et al 2015a]. Two sibs w/homozygous splice site variants had fronto-temporal pachygyria but no retinal or renal findings [Garcia-Gonzalo et al 2011]. No deletions/duplications reported. |
|
TCTN3
| 1/440 families had pathogenic variants in this gene [Bachmann-Gagescu et al 2015a]. 1/58 families (for whom known JS-genes were excluded) had biallelic pathogenic variants [Thomas et al 2012]. Homozygous truncating variants were identified in 5 pedigrees w/a severe prenatal lethal form of OFD type IV (Mohr-Majewski syndrome); however, since the phenotype also included postaxial polydactyly, cystic renal disease, bile duct proliferation, & occipital encephalocele, it is debatable whether this represents a type of OFD or MKS. 2 probands from a Turkish family w/JS, who had a homozygous missense variant, had scoliosis w/variable polydactyly, oral findings, horseshoe kidney, & ventricular septal defect [Thomas et al 2012]. No deletions/duplications reported. |
|
TMEM107
| Of 238 individuals w/JS or "OFD VI," 1 set of consanguineous twins who were homozygous for a missense variant in this gene had retinopathy & features of OFD including postaxial polydactyly; another male w/classic JS & retinopathy had compound heterozygous pathogenic variants [Lambacher et al 2016]. No deletions/duplications reported. |
|
TMEM138
| 1/440 families had pathogenic variants in this gene [Bachmann-Gagescu et al 2015a]. 11 individuals from 8 consanguineous Arab families had coloboma (6), retinal dystrophy (3), cystic kidney, or NPHP (3). Polydactyly has been observed; 1 fetus w/MKS had an encephalocele [Lee et al 2012b]. No deletions/duplications reported |
|
TMEM231
| Pathogenic variants in this gene account for some individuals w/JS of French Canadian descent. 3 persons in 2 families had a severe phenotype (lack of ambulation, aggressive behaviors, lack of independent living skills). 2 have macroscopic renal cysts & retinal disease; 1 has postaxial polysyndactyly [Srour et al 2012a]. A pathogenic gene conversion event between this gene & its pseudogene has been described [Maglic et al 2016]. |
|
TMEM237
| 1/440 families had pathogenic variants in this gene [Bachmann-Gagescu et al 2015a]. Only 2/201 individuals w/JS & 90 individuals w/MKS/JS had pathogenic variants in this gene [Huang et al 2011]. This form of JS was originally described as MKS in the Hutterite population [Boycott et al 2007], in which the carrier rate is estimated at 6% [Huang et al 2011]. Encephalocele, hydrocephalus, & cystic kidney disease are common. The "morning glory disc anomaly" has also been described in an extended family from Austria w/biallelic pathogenic variants [Janecke et al 2004, Huang et al 2011]. A 24-kb deletion including TMEM237 exon 1 & 1a extending into the adjacent gene has been identified [Watson et al 2016]. |
|
TTC21B
| To date, no individuals w/JS & biallelic pathogenic variants in this gene have been reported. The functional significance of a single (heterozygous) pathogenic variant is unknown. No clinical information was provided on 3 persons with a heterozygous change. See TTC21B, Pathogenic variants (pdf).
In a clinically diverse cohort of 753 individuals w/a ciliopathy, 5% had pathogenic variants in this gene; however, only 33% had a 2nd pathogenic variant in a different ciliopathy gene [Davis et al 2011]. |
|
ZNF423
| 1 consanguineous family w/infantile-onset NPHP, cerebellar vermis hypoplasia, & situs inversus had homozygous pathogenic missense variants in this gene; 2/96 other individuals w/JS had heterozygous changes in the gene in specific interaction domains, leading to proposed (but not proven) loss of function via a dominant-negative mechanism [Chaki et al 2012]. No deletions/duplications reported. |
