A Third Novel Locus for Primary Autosomal Recessive Microcephaly Maps to Chromosome 9q34

• Published in: American journal of human genetics Vol. 66; no. 2; pp. 724 - 727
• Main Authors: Moynihan, Leanne, Jackson, Andrew P., Roberts, Emma, Karbani, Gulshan, Lewis, Ian, Corry, Peter, Turner, Gwen, Mueller, Robert F., Lench, Nicholas J., Woods, C. Geoffrey
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.02.2000; University of Chicago Press; The American Society of Human Genetics
• Subjects: Autozygosity mapping; Biological and medical sciences; Chromosome 9q34; Chromosome Mapping; Chromosomes, Human, Pair 9 - genetics; Consanguinity; Female; Genes, Recessive - genetics; Genetic Heterogeneity; Humans; Lod Score; Male; Malformations of the nervous system; Medical sciences; Microcephaly; Microcephaly - genetics; Neurology; Pedigree; Consanguinity; Microcephaly; Autozygosity mapping; Chromosome 9q34; Genetic mapping; Human; Nervous system diseases; Linkage; Family study; Pathogenesis; Developmental disorder; Congenital disease; Mental retardation; Genetic determinism; Chromosome C9; Cerebral disorder; Genetic disease; Phenotype; Malformation; Autosomal character; Central nervous system disease; Intellectual deficiency; Recessive character
• DOI: 10.1086/302777
• ISSN: 0002-9297

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.