Two craniosynostotic syndrome loci, Crouzon and Jackson-Weiss, map to chromosome 10q23-q26

Journal Article · Thu Sep 01 04:00:00 EDT 1994 · American Journal of Human Genetics

OSTI ID:134006

Elumfa, F; Lewanda, A; Li, X ^[1]

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1. Johns Hopkins Univ., Baltimore, MD (United States); and others

Craniosynostosis is a common malformation consisting of premature fusion of skull bones leading to abnormal head shape and, in severe cases, increased intracranial pressure. Crouzon (CFD1) and Jackson-Weiss syndromes (JWS) are two distinct autosomal dominant craniosynostotic conditions with ocular proptosis and maxillary hypoplasia. In the former condition, the proptosis tends to be more severe and is due to shallow orbits. Unlike CFD1, JWS is associated with foot anomalies and highly variable phenotypic expression. We performed two point linkage and haplotype analyses with 15 markers on chromosome 10, spanning a genetic distance of 108 cM. The CFD1 locus maps to the chromosome 10q23-26 region with tightest linkage to D10S205 (Z=3.09, {theta}=0.00, 19 meioses). The JWS locus (originally described in this family) was also linked to this region in an 18 cM interval between D10S190 and D10S186. The D10S209 locus was most strongly linked (Z=11.29, {theta}=0.00, 40 meioses). All of the markers had recombinants with at least one of the conditions. Regional candidate genes implicated in craniofacial and limb development include HOX11, PAX2, ZNF32, and RBP3. These disorders may be allelic, but our data raised the possibility of genetic heterogeneity. As we gather more families, we will find evidence for or against the presence of genetically distinct forms of both syndromes. Isolation of the craniosynostotic gene(s) on chromosome 10 will be important for accurate diagnosis of these disorders and identification of genetic factors involved in craniofacial development.

• OSTI ID: 134006
• Report Number(s): CONF-941009--
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: Suppl.3 Vol. 55; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BIOLOGICAL MARKERS
CONGENITAL MALFORMATIONS
DIAGNOSIS
DOMINANT MUTATIONS
GENES
GENETIC MAPPING
HEREDITARY DISEASES
HUMAN CHROMOSOMES
PATIENTS
PHENOTYPE
SKELETAL DISEASES
STATISTICS