RGD Reference Report - DNA analysis of AHI1, NPHP1 and CYCLIN D1 in Joubert syndrome patients from the Netherlands. - Rat Genome Database

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DNA analysis of AHI1, NPHP1 and CYCLIN D1 in Joubert syndrome patients from the Netherlands.

Authors: Kroes, HY  Van Zon, PH  Fransen van de Putte, D  Nelen, MR  Nievelstein, RJ  Wittebol-Post, D  Van Nieuwenhuizen, O  Mancini, GM  Van der Knaap, MS  Kwee, ML  Maas, SM  Cobben, JM  De Nef, JE  Lindhout, D  Sinke, RJ 
Citation: Kroes HY, etal., Eur J Med Genet. 2008 Jan-Feb;51(1):24-34. Epub 2007 Oct 6.
RGD ID: 11537346
Pubmed: PMID:18054307   (View Abstract at PubMed)
DOI: DOI:10.1016/j.ejmg.2007.10.001   (Journal Full-text)

Joubert syndrome (JBS) is a clinically variable and genetically heterogeneous developmental brain disorder with autosomal recessive inheritance. Five genes, AHI1, NPHP1, CEP290, MKS3, and RPGRIP1L, and two additional loci on chromosome 9 and 11 have been identified so far. The relative contributions of AHI1 mutations and NPHP1 deletions have not yet been determined in a population-based JBS patient cohort. We therefore undertook a nationwide survey of JBS in the Netherlands and performed DNA analysis of the AHI1 and NPHP1 genes, as well as a new candidate gene CYCLIN D1. We obtained clinical data and DNA samples of 25 Dutch JBS patients. DNA analysis of AHI1 revealed pathogenic homozygous or compound heterozygous AHI1 mutations in four patients (16%). Based on the birth prevalence of about 1 in 100,000 for JBS in the Netherlands, we estimated a carrier frequency of AHI1 mutations of approximately 1 in 400. In another two patients, the AHI1 mutation Arg830Trp was identified (homozygously and heterozygously), a possible low penetrance allele. No deletions of NPHP1 or CYCLIN D1 mutations were detected in these 25 patients. In the four patients with AHI1 mutations, retinal disease (Leber congenital amaurosis or retinal dystrophy) was present in two, whereas none had renal disease. Pooling our data and data from the literature, retinal disease seems to occur in 75% of AHI1-associated JBS patients. Renal disease is present in 10% at most. We conclude that AHI1 mutations are an important cause of JBS in Dutch patients, and should always be looked for in patients suspected of JBS, especially when retinal dystrophy is present. Patients with AHI1 mutations should be regularly checked for retinal and renal disease up until adolescence.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Joubert syndrome 3  IAGP 11537346DNA:missense mutation and nonsense mutations:exon:multipleRGD 
Joubert syndrome 3  ISOAHI1 (Homo sapiens)11537346; 11537346DNA:missense mutation and nonsense mutations:exon:multipleRGD 

Objects Annotated

Genes (Rattus norvegicus)
Ahi1  (Abelson helper integration site 1)

Genes (Mus musculus)
Ahi1  (Abelson helper integration site 1)

Genes (Homo sapiens)
AHI1  (Abelson helper integration site 1)

Additional Information