Lack of large, homozygous deletions of the nephronophthisis 1 region in Joubert syndrome type B

• Published in: Pediatric nephrology (Berlin, West) Vol. 12; no. 1; pp. 16 - 19
• Main Authors: Hildebrandt, Friedhelm, Nothwang, Hans Gerd, Vossmerbäumer, Urs, Springer, Cornelia, Strahm, Brigitte, Hoppe, Bernd, Keuth, Burkhard, Fuchshuber, Arno, Querfeld, Uwe, Neuhaus, Thomas J, Brandis, Matthias
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Heidelberg Springer 01.01.1998; Springer Nature B.V
• Subjects: Anemia; Aplasia; Biological and medical sciences; Brain; Cerebellum; Children & youth; Congenital defects; Cysts; Developmental disabilities; Gene deletion; Histology; Hypotheses; Intellectual disabilities; Kidney diseases; Kidneys; Malformations of the nervous system; Malformations of the urinary system; Medical sciences; Neonates; Nephrology. Urinary tract diseases; Nephronophthisis; Neurodevelopmental disorders; Neurology; Polydactyly; Polymerase chain reaction; Polyuria; Switzerland; Germany; Human; Kidney disease; Nervous system diseases; Urinary system disease; Family study; Joubert syndrome; Juvenile nephronophtisis; Homozygosity; Chromosome 2; Genetic determinism; Cerebral disorder; Genetic disease; Heterozygosity; Malformation; Central nervous system disease; Deletion; Complex syndrome; Child
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s004670050394

Joubert syndrome type B (JSB) is a developmental disorder of the nephronophthisis (NPH) complex with multiple organ involvement, including NPH, coloboma of the eye, aplasia of the cerebellar vermis, and the facultative symptoms of psychomotor retardation, polydactyly, and neonatal tachypnea. In isolated autosomal recessive NPH type 1 (NPH1), homozygous deletions have been described as causative in more than 80% of patients. Since different combinations of the extrarenal symptoms with NPH occur in JSB, a contiguous gene deletion syndrome in the NPH1 genetic region would seem a highly likely cause for JSB. We therefore examined 11 families with JSB for the presence of extended deletions at the NPH1 locus. Genomic DNA was examined using four consecutive polymerase chain reaction (PCR) markers that are deleted in NPH1 and three PCR makers flanking the NPH1 deletion. In all seven markers examined, there was no homozygous deletion detected in any of the 11 JSB families studied. Since these markers saturate the NPH1 deletion region at high density, this finding excludes the presence of large homozygous deletions of the NPH1 region in these JSB families, making it unlikely that deletions of the NPH1 region are a primary cause for JSB. [PUBLICATION ABSTRACT]