Mutation analysis of NPHP6/CEP290 in patients with Joubert syndrome and Senior-Løken syndrome.
BACKGROUND
Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease that constitutes the most common genetic cause of renal failure in the first three decades of life. Using positional cloning, six genes (NPHP1-6) have been identified as mutated in NPHP. In Joubert syndrome (JBTS), NPHP may be associated with cerebellar vermis aplasia/hypoplasia, retinal degeneration and mental retardation. In Senior-Løken syndrome (SLSN), NPHP is associated with retinal degeneration. Recently, mutations in NPHP6/CEP290 were identified as a new cause of JBTS.


METHODS
Mutational analysis was performed on a worldwide cohort of 75 families with SLSN, 99 families with JBTS and 21 families with isolated nephronophthisis.


RESULTS
Six novel and six known truncating mutations, one known missense mutation and one novel 3 bp pair in-frame deletion were identified in a total of seven families with JBTS, two families with SLSN and one family with isolated NPHP.
Helou
Juliana
J
Otto
Edgar A
EA
Attanasio
Massimo
M
Allen
Susan J
SJ
Parisi
Melissa A
MA
Glass
Ian
I
Utsch
Boris
B
Hashmi
Seema
S
Fazzi
Elisa
E
Omran
Heymut
H
O'Toole
John F
JF
Sayer
John A
JA
Hildebrandt
Friedhelm
F
D000951:Antigens, Neoplasm / Q000235:genetics*; D001483:Base Sequence; D018797:Cell Cycle Proteins; D015331:Cohort Studies; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D010641:Phenotype; D051437:Renal Insufficiency / Q000235:genetics; D013577:Syndrome
D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; C493903:Cep290 protein, human; D003598:Cytoskeletal Proteins; D009363:Neoplasm Proteins