| Full gene name: | RPGRIP1-like |
|---|---|
| Entrez Gene ID: | 23322 |
| Location: | 16q12.2 |
| Synonyms: | NPHP8, MKS5, JBTS7, FTM, CORS3 |
| Type: | protein-coding |
SNPs given by the user that are near or inside this gene:
| SNP | Distance (bp) | Direction |
|---|---|---|
| rs9939609 | 82756 | upstream |
The protein encoded by this gene can localize to the basal body-centrosome complex or to primary cilia and centrosomes in ciliated cells. The encoded protein has been found to interact with nephrocystin-4. Defects in this gene are a cause of Joubert syndrome type 7 (JBTS7) and Meckel syndrome type 5 (MKS5). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
| OMIM ID: | `OMIM ID 610937 `_ |
|---|
Allelic Variants (Selected Examples)
.0001 JOUBERT SYNDROME 7
In a French patient with Joubert syndrome (JBTS7; 611560), Delous et al. (2007) identified compound heterozygosity for 2 mutations in the RPGRIP1L gene: a 697A-T transversion in exon 6 resulting in a lys233-to-ter (K233X) substitution, and a T615P (610937.0002) mutation. The child had mental retardation, cerebellar ataxia, nephronophthisis, oculomotor apraxia, ptosis, and genu valgum. End-stage renal disease occurred at age 6 years.
.0002 JOUBERT SYNDROME 7
In a French patient with Joubert syndrome (JBTS7; 611560), Delous et al. (2007) identified compound heterozygosity for 2 mutations in the RPGRIP1L gene: a 1843A-C transversion in exon 15 of the RPGRIP1L gene resulting in a thr615-to-pro (T615P) substitution and a K233X (610937.0001) mutation. A second unrelated French patient with a similar phenotype was compound heterozygous for T615P and Q253X (610937.0003).
Brancati et al. (2008) reported a brother and sister with Joubert syndrome who were homozygous for the T615P mutation. Both presented with developmental delay, growth and mental retardation, nephronophthisis, and severe scoliosis. Visual acuity, fundus examination, and liver function were normal. There was clinical variability between the 2 sibs regarding some features, with the sister being more severely affected. She died at age 17.5 years from renal failure, while he was still alive at age 22 years after kidney transplant. Both had the molar tooth sign on MRI.
.0003 JOUBERT SYNDROME 7
In a French patient with Joubert syndrome (JBTS7; 611560), Delous et al. (2007) identified compound heterozygosity for 2 mutations in the RPGRIP1L gene: a 757C-T transition in exon 6 resulting in a gln253-to-ter (Q253X) substitution and a T615P (610937.0002) mutation. The patient had mental retardation, cerebellar ataxia, nephronophthisis, oculomotor apraxia, the molar tooth sign, ptosis, and scoliosis.
.0004 JOUBERT SYNDROME 7
In 2 French sibs with Joubert syndrome (JBTS7; 611560), Delous et al. (2007) identified a homozygous 2083G-C transversion in exon 15 of the RPGRIP1L gene, resulting in an ala695-to-pro (A695P) substitution. Both sibs had scoliosis, oculomotor apraxia, nystagmus, the molar tooth sign, and nephronophthisis with end-stage renal disease by age 9 years. Only 1 had mild mental retardation.
.0005 MECKEL SYNDROME, TYPE 5
In 2 presumably related Moroccan fetuses diagnosed with Meckel syndrome (MKS5; 611561) at 15 to 16 weeks’ gestation by ultrasound, Delous et al. (2007) identified a homozygous 394A-T transversion in exon 4 of the RPGRIP1L gene, resulting in an arg132-to-ter (R132X) substitution. Post-termination examination showed anencephaly, occipital encephalocele, postaxial polydactyly, cleft lip and palate, microphthalmia, cystic kidney disease, and hepatic bile duct proliferation. One fetus showed bowing of the long bones. The severe phenotype corresponded to the complete loss of RPGRIP1L function.
.0006 MECKEL SYNDROME, TYPE 5
In a French fetus diagnosed with Meckel syndrome (MKS5; 611561) at 16 weeks’ gestation by ultrasound, Delous et al. (2007) identified compound heterozygosity for 2 truncation mutations in the RPGRIP1L gene: a 1033C-T transition in exon 9 resulting in a gln345-to-ter (Q345X) substitution, and a 2614C-T transition in exon 17 resulting in a gln872-to-ter (Q872X; 610937.0007) substitution. Post-termination examination showed anencephaly, occipital encephalocele, postaxial polydactyly, cleft lip and palate, microphthalmia, cystic kidney disease, hepatic bile duct proliferation, and bowing of the long bones. The severe phenotype corresponded to the complete loss of RPGRIP1L function.
.0007 MECKEL SYNDROME, TYPE 5
See 610937.0006 and Delous et al. (2007).
.0008 JOUBERT SYNDROME 7
In a Turkish girl with Joubert syndrome (JBTS7; 611560), born of consanguineous parents, Arts et al. (2007) identified a homozygous 1-bp deletion (1721delA) in the RPGRIP1L gene, resulting in a frameshift and premature protein truncation before the C2 domain. The 10-year-old girl had molar tooth sign, hypotonia, ataxia, mental retardation, abnormal eye movements, and renal disease. Retinal disease was not present.
.0009 JOUBERT SYNDROME 7
In a patient with Joubert syndrome (JBTS7; 611560), Arts et al. (2007) identified compound heterozygosity for 2 mutations in the RPGRIP1L gene: a 2050C-T transition, resulting in a gln684-to-ter (Q684X) substitution, and a T615P (610937.0002) mutation. The Q684X mutation was predicted to truncate the protein before the C2 domain. In vitro functional expression studies showed that both mutant proteins disrupted NPHP4 binding. At age 5, the child had the molar tooth sign, hypotonia, ataxia, mental retardation, abnormal eye movements, postaxial polydactyly, and encephalocele. Renal and retinal disease were not present.
.0010 JOUBERT SYNDROME 7
In a Moroccan girl with Joubert syndrome (611560), born of consanguineous parents, Brancati et al. (2008) identified a homozygous 1-bp deletion (2268delA) in exon 16 of the RPGRIP1L gene, resulting in a frameshift and premature protein truncation. She had episodes of hyperpnea and apnea and delayed milestones. At age 1 year, she developed renal dysfunction associated with small kidneys with increased echogenicity, loss of corticomedullary differentiation, and multiple cysts compatible with nephronophthisis. At age 4 years, she had chronic renal failure, marked growth retardation, and severe psychomotor delay with lack of head control and inability to speak any meaningful word. The molar tooth sign was present on MRI.
.0011 COACH SYNDROME
In a 17-year-old male with COACH syndrome (216360), defined as Joubert syndrome (611560) with liver involvement, Doherty et al. (2010) identified compound heterozygosity for 2 mutations in the RPGRIP1L gene: a 2413C-T transition, resulting in an arg805-to-ter (R805X) substitution, and a 1975T-C transition, resulting in a ser659-to-pro (S659P; 610937.0012) substitution. The patient had abnormal breathing pattern, mental retardation, molar tooth sign on brain MRI, congenital hepatic fibrosis with bile dule abnormalities, and nephronophthisis requiring renal transplant.
.0012 COACH SYNDROME
See 610937.0011 and Doherty et al. (2010).
.0013 RETINITIS PIGMENTOSA IN CILIOPATHIES, MODIFIER OF
Khanna et al. (2009) presented evidence that a common allele in the RPGRIP1L gene, a 685G-A transition, resulting in an ala229-to-thr (A229T) substitution (rs61747071), may be a modifier of retinal degeneration in patients with ciliopathies due to other mutations. The 229T allele was significantly enriched among a group of 487 patients with ciliopathy and retinal pigmentosa, including LCA (204000), Senior-Loken syndrome (266900), Joubert syndrome (213300), and BBS (209900), compared to 115 patients with ciliopathy without retinal pigmentosa, including NPHP (256100) and MKS (249000) (p = 1.66 x 10(-5)). In vitro functional expression studies showed that the 229T allele had decreased ability to bind to RPGR compared to the 229A allele.
No pathways found linked to this gene.
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