Biomedical subjects

Philip D Cotter

Publications and source records attributed to Philip D Cotter.

21 records · Page 2Linked to original sources

PubMed2003

A multiplex methylation PCR assay for identification of uniparental disomy of chromosome 7.

Uniparental disomy of chromosome 7 (UPD7) is associated with abnormal phenotypic effects because of inappropriate expression of imprinted genes on chromosome 7. Based on the differential methylation of the promoter region of the imprinted PEG1/MEST locus at 7q32, we designed a multiplex methylation PCR (mPCR) assay to rapidly distinguish UPD7 from biparental inheritance of chromosome 7. Primers were designed to produce different sized PCR amplicons based on the parent of origin-specific methylation at this locus; electrophoresis of PCR amplicons showed a 189-bp product from the methylated maternal allele and a 109-bp product from the unmethylated paternal allele. This mPCR assay correctly predicted the chromosome 7 imprinting status in normal control and UPD7 samples. Previous assays for UPD7 required genotyping of the proband and parents, or separate maternal- and paternal-specific mPCR reactions. The advantage of this assay is that parental samples are not required and that amplification of both alleles in the same reaction is simpler and provides an internal control. This multiplex mPCR assay will be useful in screening for UPD7 in patients with Silver-Russell syndrome (SRS; also Russell-Sliver syndrome, RSS), primordial growth retardation, and in patients with supernumerary marker chromosomes or chromosome rearrangements of chromosome 7 origin.

Alleles↗

PubMed2003

Fertility in a female with mosaic trisomy 8.

OBJECTIVE: To describe the first term pregnancy in a patient with the characteristic features of trisomy 8 mosaicism. DESIGN: Case report. SETTING: University department. PATIENT(S): The 23-year-old proband had a history of cleft palate, mixed bilateral hearing loss, short stature, and developmental delay. She had dysmorphic craniofacial features, mild musculoskeletal abnormalities, and abnormal skin pigmentation. Her karyotype was mos47,XX,+8[17]/46,XX[83]. INTERVENTION(S): Cytogenetic analysis and genetics evaluation of the proband and her child. MAIN OUTCOME MEASURE(S): The first successful pregnancy in a phenotypically abnormal trisomy 8 patient. RESULT(S): The pregnancy was largely uncomplicated except for an abnormal triple screen, with subsequent normal amniocentesis, and a fetal ultrasound revealing a clubfoot anomaly. Cytogenetic analysis of the child showed a 46,XX karyotype. CONCLUSION(S): Our review indicates that reproduction in females with mosaic trisomy 8 is possible, albeit uncommon. Until additional cases are reported and any specific risks identified, prenatal diagnosis of any pregnancies in mosaic trisomy 8 patients would seem prudent. In addition, this and previous cases illustrate the need to effectively counsel families of mosaic trisomy 8 children about the possibility of reproduction.

Adult↗

PubMed2002

Additional patient with del(12)(q21.2q22): further evidence for a candidate region for cardio-facio-cutaneous syndrome?

Cardio-facio-cutaneous (CFC) syndrome is characterized by a distinct facial appearance, cardiac defects, ectodermal anomalies and developmental delay. Recently, we reported a 19-month-old girl with phenotypic manifestations consistent with the CFC syndrome who had an interstitial deletion of the long arm of chromosome 12, del(12)(q21.2q22), implicating a possible locus for CFC syndrome. Here, we report an additional patient with a cytogenetically identical interstitial deletion: 47,XYY,del(12)(q21.2q22). To further characterize this deletion we used microarray-based comparative genomic hybridization (array CGH). Array CGH confirmed both the deletion and the second Y chromosome. The deletion on chromosome 12q spanned at least 14 Mb as indicated by the positions on the genome sequence of the 4 BAC clones included in the deletion. While the proband did not have the classic features of CFC, he had some dysmorphic craniofacial characteristics, ectodermal anomalies and moderate developmental delay which were suggestive of CFC syndrome; however, this patient did not have classical CFC. The phenotypic differences between the two del(12)(q21.2q22) patients may be due to variability in the expression of the syndrome, or this deletion may present as a syndrome with overlapping features. Alternatively, the phenotypic differences may result from discordance at the molecular level, which may yield a critical minimal region of deletion for CFC. The region 12q21.2 --> q22 remains a possible candidate region for CFC syndrome. Additional characterization of these and other CFC patients may confirm and further refine this candidate region.

Abnormalities, Multiple↗