Paternal uniparental isodisomy for chromosome 14 with mosaicism for a supernumerary marker chromosome 14

Abstract

Uniparental disomy (UPD) describes the inheritance of two homologous chromosomes from a single parent. Disease phenotypes associated with UPD and chromosomal imprinting, rather than with mutations, include Beckwith-Wiedemann syndrome (paternal UPD11p), Angelman syndrome (paternal UPD15), Prader-Willi syndrome (maternal UPD15), and transient neonatal diabetes (paternal UPD6). Here we report on the first case of paternal uniparental isodisomy of chromosome 14 with a mosaicism for a supernumerary marker chromosome 14. The patient demonstrated a small thorax with a 'coat hanger' shape of the ribs, kyphoscoliosis, hypoplasia of the maxilla and mandible, a broad nasal bridge with anteverted nares, contractures of the wrists with ulnar deviation bilaterally, diastasis recti, and marked muscle hypotonia. Vertical skin creases under the chin and stippled epiphyses of the humeri were features not previously described in patients with paternal UPD14. This case illustrates that as with the finding of an isochromosome, a supernumerary marker chromosome can be an important clue to the presence of UPD14.

Complex and segmental uniparental disomy updated

“…Furthermore, three cases with UPD 14 and mosaicism for an SMC(14) were reported 120 141. The first was a female with the typical findings of paternal UPD 14 141. The second and the third were males and showed maternal heterodisomy 14 120.…”

“…So, maternal UPD 12 appears also to be without phenotypical effects. Furthermore, three cases with UPD 14 and mosaicism for an SMC(14) were reported 120 141. The first was a female with the typical findings of paternal UPD 14 141.…”

Low‐level mosaicism of trisomy 14: Phenotypic and molecular characterization

“…Mosaicism originating from a trisomic zygote can result in UPD, a phenomenon that is relevant to trisomy 14 mosaicism because of the presence of imprinted genes on chromosome 14. However, up until now the UPD has been described in association with mosaic trisomy 14 in only one patient with supernumerary marker chromosome 14 but it has not been tested in the majority of the reported cases [Mattes et al, 2007]. In Patient #1 the STR analysis ruled out this possibility and showed a biparental inheritance in the disomic cells.…”

Prenatal findings and epimutations for paternal uniparental disomy for chromosome 14 syndrome

“…Paternal uniparental disomy for chromosome 14 (UPD(14)pat) is usually associated with severe polyhydramnios, a small bell‐shaped thorax, dysmorphic facial features, skeletal abnormalities, abdominal wall defects, muscular hypotonia, developmental delay, and poor prognosis . Previous reports indicate that chromosome‐14 isochromosome or a chromosome‐14 Robertsonian translocation are indicative of UPD(14)pat .…”

“…Epimutation for UPD(14)pat syndrome is caused by hypermethylation of both the intergenic differentially methylated region (IG‐DMR) and the MEG3‐DMR. On ultrasonography during the second and third trimesters, prenatal presentation of UPD(14)pat syndrome includes a small bell‐shaped thorax with a ‘coat‐hanger’ appearance and polyhydramnios . In the present study we used magnetic resonance imaging (MRI) to examine prenatal presentation in a case of epimutation‐associated UPD(14)pat syndrome.…”