Abstract
A consanguineous pedigree is described where 14 individuals are affected with a novel autosomal recessive disorder, which causes static moderate mental retardation, truncal obesity, a congenital nonprogressive retinal dystrophy and micropenis in males. We have tentatively named this condition MORM syndrome. It shows similarities to Bardet–Biedl syndrome and Cohen syndrome, but can be distinguished by clinical features; the age of onset and nonprogressive nature of the visual impairment, the lack of characteristic facies, skin or gingival infection, microcephaly, ‘mottled retina’, polydactyly and small penis without testicular anomalies. Furthermore, linkage to the known Bardet–Biedl (BBS1–8) and Cohen syndrome loci was excluded. Autozygosity mapping identified a single homozygous subtelomeric region shared by all affecteds on chromosome 9q34.3, with a maximum LOD score of 5.64. We believe this to be the first example of the identification of a subtelomeric recessive locus by autozygosity mapping.
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Acknowledgements
We thank the family members and their physicians who helped with this study. DJH is supported by the Medical Research Council. KS, ER, HJ, JB and CGW are supported by the Wellcome Trust.
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Electronic-Database Information: Online Mendelian Inheritance of Man (OMIM) for clinical and genetic information on Bardet–Biedl syndrome (209900) and Cohen syndrome (216550):
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
Genome Database (GDB) for polymorphic microsatellite data:
Human Genome Browser for loci, gene, polymorphic marker and SNP physical location data for the human genome:
http://genome.cse.ucsc.edu/cgi-bin/hgGateway?org=human
Center for Medical Genetics for the Marshfield Linkage Maps:
http://research.marshfieldclinic.org/genetics/Map_Markers/maps/IndexMapFrames.html
Primer3 for design of novel microsatellite repeat markers:
http://www-genome.wi.mit.edu/cgi-bin/primer/primer3_www.cgi BLAST 2 for SNP sequence analysis:
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Hampshire, D., Ayub, M., Springell, K. et al. MORM syndrome (mental retardation, truncal obesity, retinal dystrophy and micropenis), a new autosomal recessive disorder, links to 9q34. Eur J Hum Genet 14, 543–548 (2006). https://doi.org/10.1038/sj.ejhg.5201577
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DOI: https://doi.org/10.1038/sj.ejhg.5201577
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