SHORT REPORT

Homozygosity mapping of a third Joubert syndrome locus to 6q23

C Lagier-Tourenne¹, E Boltshauser², N Breivik³, M Gribaa¹, C Bétard⁴, C Barbot⁵, M Koenig¹

¹ IGBMC, CNRS/INSERM/ULP, Illkirch, C.U. de Strasbourg, France
² Department of Neurology, Children’s University Hospital, Zürich, Switzerland
³ Department of Paediatrics, Aalesund Hospital, Aalesund, Norway
⁴ Centre National de Génotypage, Evry, France
⁵ Department of Neurology, Hospital Maria Pia, Porto, Portugal

Correspondence to:
Correspondence to:
Professor M Koenig
Institut de Génétique et de Biologie Moléculaire et Cellulaire, 1 rue Laurent Fries BP10142, 67404 Illkirch cedex, C.U. de Strasbourg, France; mkoenig{at}igbmc.u-strasbg.fr

Background: Joubert syndrome (JS) is a recessively inherited disorder characterised by hypotonia at birth and developmental delay, followed by truncal ataxia and cognitive impairment, characteristic neuroimaging findings (cerebellar vermis hypoplasia, "molar tooth sign") and suggestive facial features. JS is clinically heterogeneous with some patients presenting with breathing abnormalities in the neonatal period, oculomotor apraxia, retinal dystrophy, retinal coloboma, ptosis, hexadactyly, and nephronophtisis or cystic dysplastic kidneys. JS is also genetically heterogeneous, with two known loci, on 9q34 (JBTS1) and 11p11-q12 (CORS2), representing only a fraction of cases.

Methods: A large consanguineous Joubert family (five affected) was analysed for linkage with a marker set covering the entire genome and 16 smaller families were subsequently tested for candidate loci.

Results: We report here the identification of a third locus in 6q23 (JBTS3) from the study of two consanguineous families. LOD score calculation, including the consanguinity loops, gave a maximum value of 4.1 and 2.3 at q = 0 for the two families, respectively.

Conclusions: Linkage between the disease and the D6S1620–D6S1699 haplotype spanning a 13.1 cM interval is demonstrated. Genotype-phenotype studies indicate that, unlike CORS2, JBTS3 appears not to be associated with renal dysfunction.

Keywords: cerebellar ataxia; cerebello-oculo-renal syndromes; homozygosity mapping; Joubert syndrome; molar tooth sign

Abbreviations: CORS, cerebello-oculo-renal syndrome; JS, Joubert syndrome

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