Copyright © 2000 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 66, Issue 2, 724-727, 1 February 2000
doi:10.1086/302777
Report
A Third Novel Locus for Primary Autosomal Recessive Microcephaly Maps to Chromosome 9q34
Leanne Moynihan1, Andrew P. Jackson1, 2, Emma Roberts1, Gulshan Karbani2, Ian Lewis3, Peter Corry4, Gwen Turner2, Robert F. Mueller1, 2, Nicholas J. Lench1, * and C. Geoffrey Woods1, 2, 
, 
1 Molecular Medicine Unit, St. James’s University Hospital, Leeds
2 Department of Clinical Genetics, St. James’s University Hospital, Leeds
3 Department of Paediatric Oncology and Haematology, St. James’s University Hospital, Leeds
4 Department of Paediatrics, St. Lukes Hospital, Bradford, United Kingdom
Address for correspondence and reprints: Dr. C. G. Woods, Department of Clinical Genetics, St. James’s University Hospital, Leeds LS9 7TF, United Kingdom* Present affiliation: Oxagen Limited, Abingdon, Oxford.
Abstract
Primary autosomal recessive microcephaly is a clinical diagnosis of exclusion in an individual with a head circumference ⩾4 SDs below the expected age-and-sex mean. There is associated moderate mental retardation, and neuroimaging shows a small but structurally normal cerebral cortex. The inheritance pattern in the majority of cases is considered to be autosomal recessive. Although genetic heterogeneity for this clinical phenotype had been expected, this has only recently been demonstrated, with the mapping of two loci for autosomal recessive primary microcephaly: MCPH1 at 8p and MCPH2 at 19q. We have studied a large multiaffected consanguineous pedigree, using a whole-genome search, and have identified a third locus, MCPH3 at 9q34. The minimal critical region is ∼12 cM, being defined by the markers cen-D9S1872-D9S159-tel, with a maximum two-point LOD score of 3.76 (recombination fraction 0) observed for the marker D9S290.
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