TY - JOUR
T1 - Homozygosity mapping in families with Joubert syndrome identifies a locus on chromosome 9q34.3 and evidence for genetic heterogeneity
AU - Saar, Kathrin
AU - Al-Gazali, Lihadh
AU - Sztriha, László
AU - Rueschendorf, Franz
AU - Nur-E-Kamal, Mohammed
AU - Reis, André
AU - Bayoumi, Riad
N1 - Funding Information:
We thank Michaela Seeger for excellent technical assistance, Gudrun Nürnberg for help with graphics, and Professor Karl Sperling for continued encouragement and support. The financial support from the Deutscher Akademischer Austausch Dienst (DAAD) to R.B. is gratefully acknowledged. The Mikrosatellitenzentrum is supported by a grant-in-aid from the German Genome Project to A.R.
PY - 1999
Y1 - 1999
N2 - Joubert syndrome is a rare developmental defect of the cerebellar vermis, with autosomal recessive inheritance. The phenotype is highly variable and may include episodic hyperpnea, abnormal eye movements, hypotonia, ataxia, developmental delay, and mental retardation. Even within sibships the phenotype may vary, making it difficult to establish the exact clinical diagnostic boundaries of Joubert syndrome. To genetically localize the gene region, we have performed a whole-genome scan in two consanguineous families of Arabian/Iranian origins, with multiple affected probands. In one family, we detected linkage to the telomeric region of chromosome 9q, close to the marker D9S158, with a multipoint LOD score of Z = +3.7. The second family did not show linkage to this region, giving a first indication of genetic heterogeneity underlying Joubert syndrome. These findings were supported by subsequent analysis of two smaller families - one compatible with linkage to 9q; the other, unlinked. We conclude that Joubert syndrome is clinically and genetically heterogeneous and that one locus maps to chromosome 9q.
AB - Joubert syndrome is a rare developmental defect of the cerebellar vermis, with autosomal recessive inheritance. The phenotype is highly variable and may include episodic hyperpnea, abnormal eye movements, hypotonia, ataxia, developmental delay, and mental retardation. Even within sibships the phenotype may vary, making it difficult to establish the exact clinical diagnostic boundaries of Joubert syndrome. To genetically localize the gene region, we have performed a whole-genome scan in two consanguineous families of Arabian/Iranian origins, with multiple affected probands. In one family, we detected linkage to the telomeric region of chromosome 9q, close to the marker D9S158, with a multipoint LOD score of Z = +3.7. The second family did not show linkage to this region, giving a first indication of genetic heterogeneity underlying Joubert syndrome. These findings were supported by subsequent analysis of two smaller families - one compatible with linkage to 9q; the other, unlinked. We conclude that Joubert syndrome is clinically and genetically heterogeneous and that one locus maps to chromosome 9q.
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U2 - 10.1086/302655
DO - 10.1086/302655
M3 - Article
C2 - 10577920
AN - SCOPUS:0033358738
SN - 0002-9297
VL - 65
SP - 1666
EP - 1671
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 6
ER -