RESUMO
Primary ciliary dyskinesia (PCD) is associated with abnormal organ positioning (situs) and congenital heart disease (CHD). This study investigated genotype-phenotype associations in PCD to facilitate risk predictions for cardiac and laterality defects. This retrospective cohort study of 389 UK patients with PCD found 51% had abnormal situs and 25% had CHD and/or laterality defects other than situs inversus totalis. Patients with biallelic mutations in a subset of nine PCD genes had normal situs. Patients with consanguineous parents had higher odds of situs abnormalities than patients with non-consanguineous parents. Patients with abnormal situs had higher odds of CHD and/or laterality defects.
Assuntos
Anormalidades Múltiplas/epidemiologia , Transtornos da Motilidade Ciliar/epidemiologia , Cardiopatias Congênitas/epidemiologia , Situs Inversus/epidemiologia , Anormalidades Múltiplas/genética , Transtornos da Motilidade Ciliar/genética , Consanguinidade , Feminino , Predisposição Genética para Doença , Genótipo , Cardiopatias Congênitas/genética , Humanos , Masculino , Mutação , Fenótipo , Prevalência , Estudos Retrospectivos , Fatores de Risco , Situs Inversus/genética , Reino Unido/epidemiologiaRESUMO
Infantile hypertrophic pyloric stenosis (IHPS) is the most common inherited form of gastrointestinal obstruction in infancy. The disease is considered a paradigm for the sex-modified model of multifactorial inheritance and affects males four times more frequently than females. However, extended pedigrees consistent with autosomal dominant inheritance have been documented. We have analysed data from an extended IHPS family including eight affected individuals (five males and three females) and mapped the disease locus to chromosome 16q24 (LOD score=3.7) through an SNP-based genome wide scan. Fourteen additional multiplex pedigrees did not show evidence of linkage to this region, indicating locus heterogeneity.
