title: Genetic heterogeneity in LEOPARD syndrome: two families with no mutations in PTPN11.
abstract: LEOPARD syndrome (lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, and sensorineural deafness) is an autosomal dominant condition. The main clinical features include multiple lentigines, cardiovascular defects, and facial anomalies, some of which are shared with Noonan syndrome (NS). Recent reports have shown that LEOPARD syndrome can be caused by mutations in PTPN11, the gene in which mutations can produce NS. Here we report the findings of mutation screening and linkage analysis of PTPN11 in three families with LEOPARD syndrome. We identified a novel mutation in one family. The mutation (1529A>C) substitutes proline for glutamine at amino acid 510 (Gln510Pro). No variations in sequence were observed in the other two families, and negative LOD scores excluded linkage to the PTPN11 locus, showing that LEOPARD syndrome is genetically heterogeneous.
authors.affiliation: Medical Genetics Unit, Department of Clinical Developmental Sciences, St. George's Hospital Medical School, London, SW17 0RE, UK.
authors.forename: Kamini
authors.initials: K
authors.lastname: Kalidas
authors.affiliation: Medical Genetics Unit, Department of Clinical Developmental Sciences, St. George's Hospital Medical School, London, SW17 0RE, UK.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Shaw
authors.affiliation: Medical Genetics Unit, Department of Clinical Developmental Sciences, St. George's Hospital Medical School, London, SW17 0RE, UK.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Crosby
authors.affiliation: Clinical Genetics Service, Bristol Royal Hospital for Sick Children, Bristol, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Newbury-Ecob
authors.affiliation: Clinical Genetics Service, Bristol Royal Hospital for Sick Children, Bristol, UK.
authors.forename: Lynn
authors.initials: L
authors.lastname: Greenhalgh
authors.affiliation: Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK.
authors.forename: Isabel K
authors.initials: IK
authors.lastname: Temple
authors.affiliation: Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Law
authors.affiliation: Medical Genetics Unit, Department of Clinical Developmental Sciences, St. George's Hospital Medical School, London, SW17 0RE, UK.
authors.forename: Amisha
authors.initials: A
authors.lastname: Patel
authors.affiliation: Medical Genetics Unit, Department of Clinical Developmental Sciences, St. George's Hospital Medical School, London, SW17 0RE, UK.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Patton
authors.affiliation: Medical Genetics Unit, Department of Clinical Developmental Sciences, St. George's Hospital Medical School, London, SW17 0RE, UK. sggt100@sghms.ac.uk.
authors.forename: Steve
authors.initials: S
authors.lastname: Jeffery
mesh_terms: D000293:Adolescent; D019943:Amino Acid Substitution; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D044542:LEOPARD Syndrome / Q000201:enzymology* / Q000235:genetics*; D008297:Male; D009154:Mutation; D009634:Noonan Syndrome / Q000201:enzymology / Q000235:genetics; D010375:Pedigree; D017354:Point Mutation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases / Q000235:genetics*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D004247:DNA; C516724:PTPN11 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D017027:Protein Tyrosine Phosphatases