Description, nomenclature, and mapping of a novel cerebello-renal syndrome with the molar tooth malformation.
Cerebello-oculo-renal syndromes (CORSs) and Joubert syndrome (JS) are clinically and genetically heterogeneous autosomal recessive syndromes that share a complex neuroradiological malformation resembling a molar tooth on brain axial images, a condition referred to as "molar tooth on imaging" (MTI) or the "molar tooth sign." The current literature on these syndromes is complex, with overlapping and incomplete phenotypes that complicate the selection of clinically homogeneous cases for genetic purposes. So far, only one locus (JBTS1 on 9q34) has been mapped, in two families with JS. Here, we describe a large consanguineous family with JS and nephronophthisis, representing a novel cerebello-renal phenotype. We have mapped this condition to the pericentromeric region of chromosome 11 and have named the locus "CORS2." The acronym "CORS" is proposed for all loci associated with JS, CORSs, and related phenotypes sharing the MTI, because this neuroradiological sign seems to be the unifying feature of these clinically heterogeneous syndromes.
Valente
Enza Maria
EM
IRCCS CSS, San Giovanni Rotondo and CSS Mendel, Rome, Italy. e.valente@css-mendel.it
Salpietro
Damiano Carmelo
DC
Brancati
Francesco
F
Bertini
Enrico
E
Galluccio
Tiziana
T
Tortorella
Gaetano
G
Briuglia
Silvana
S
Dallapiccola
Bruno
B
D000015:Abnormalities, Multiple / Q000145:classification / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D002531:Cerebellum / Q000002:abnormalities* / Q000473:pathology; D002648:Child; D002880:Chromosomes, Human, Pair 11; D005124:Eye Abnormalities; D005260:Female; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D010375:Pedigree; D013577:Syndrome