Robin M Winter

The association of the Noonan phenotype with neurofibromatosis type 1 (NF1) was first noted by Allanson et al. [Am J Med Genet 1985;21:457-462.] and 30 further cases have subsequently been reported. It has been suggested that this phenotype is more common than previously appreciated, as Colley et al. [Clin Genet 1996;49:59-64.] examined 94 sequentially identified patients with NF1 from their genetic register and found Noonan features in 12. A 3-bp deletion of exon 17 of the NF1 ...

Fraser syndrome (OMIM 219000) is a multisystem malformation usually comprising cryptophthalmos, syndactyly and renal defects1. Here we report autozygosity mapping and show that the locus FS1 at chromosome 4q21 is associated with Fraser syndrome, although the condition is genetically heterogeneous. Mutation analysis identified five frameshift mutations in FRAS1, which encodes one member of a family of novel proteins related to an extracellular matrix (ECM) blastocoelar protein found in ...

Nonsyndromic cleft lip with or without cleft palate (CL/P) is a common craniofacial developmental defect. Recent segregation analyses have suggested that major genes play a role in the etiology of CL/P. Linkage to 22 candidate genes was tested in 11 multigenerational families with CL/P, and 21 of these candidates were excluded. APOC2, 19q13.1, which is linked to the proto-oncogene BCL3, gave suggestive evidence for linkage to CL/P. The study was expanded to include a total of 39 ...

Mutations in the fibroblast growth factor receptor 2 (FGFR2) gene have been identified in Crouzon syndrome, an autosomal dominant condition causing premature fusion of the cranial sutures (craniosynostosis). A mutation in FGFR1 has been established in several families with Pfeiffer syndrome, where craniosynostosis is associated with specific digital abnormalities. We now report point mutations in FGFR2 in seven sporadic Pfeiffer syndrome patients. Six of the seven Pfeiffer syndrome ...

Angelman syndrome (AS) is an imprinted neurobehavioral disorder characterized by mental retardation, absent speech, excessive laughter, seizures, ataxia, and a characteristic EEG pattern. Classical lesions, including deletion, paternal disomy, or epigenetic mutation, are confirmatory of AS diagnoses in 80% of cases. Loss-of-function mutations of the UBE3A gene have been identified in approximately 8% of AS cases, failing to account for the remaining patient population, and there appears ...

Mutations in the fibroblast growth factor receptor 2 (FGFR2) gene have previously been identified in Crouzon syndrome, an autosomal dominant condition involving premature fusion of the cranial sutures. Several different missense and other mutations have been identified in Crouzon syndrome patients, clustering around the third immunoglobulin-like domain. We report here the identification of a mutation in the transmembrane region of FGFR3, common to three unrelated patients with classical ...

Opitz (or G/BBB) syndrome is a pleiotropic genetic disorder characterized by hypertelorism, hypospadias, and additional midline defects. This syndrome is heterogeneous with an X-linked (XLOS) and an autosomal dominant (ADOS) form. The gene implicated in the XLOS form, MID1, encodes a protein containing a RING-Bbox-Coiled-coil motif belonging to the tripartite motif (TRIM) family. To further clarify the molecular basis of XLOS, we have undertaken mutation analysis of the MID1 gene in ...

The causative relationship between several of the syndromic forms of craniosynostosis and mutations in the fibroblast growth factor receptor (FGFR) loci is now well established. However, within the group of patients with craniosynostosis, there are several families and sporadic cases whose clinical features differ in variable degrees from the classically described syndromes of craniosynostosis. In this communication we present novel FGFR2 mutations associated with a spectrum of ...

BACKGROUND: No explanation for moderate to severe mental retardation is apparent in about 40% of cases. Although small chromosomal rearrangements may account for some undiagnosed cases, a lack of genome-wide screening methods has made it impossible to ascertain the frequency of such abnormalities.

METHODS: A fluorescence in-situ hybridisation (FISH) test was used to examine the integrity of chromosome ends in 284 children with unexplained moderate to severe retardation, and in 182 ...