Paternal uniparental disomy for chromosome 14: A case report and review

Abstract

Uniparental disomy (UPD) for several chromosomes has been associated with disease phenotypes. Maternal UPD for chromosome 14 has been described and has a characteristic abnormal phenotype. Paternal UPD14 is rare and only three previous cases have been reported. We describe a new case of paternal UPD for chromosome 14 in an infant with a 45,XX,der(13q;14q) karyotype, which was confirmed by molecular analysis. The proposita had findings similar to those of the previous cases of patUPD14 and we conclude that there is a characteristic patUPD14 syndrome most likely due to imprinting effects. Couples with Robertsonian translocations involving chromosome 14 should be counseled as to the possibility of UPD14 and the option of prenatal diagnosis when indicated.

Inhibition of adipogenesis and development of glucose intolerance by soluble preadipocyte factor–1 (Pref-1)

“…Paternal monoallelic expression of pref-1/dlk1 has been observed in the syntenic chromosomes 12, 18, and 14 in mice, sheep, and humans, respectively (18-20, 43, 44). Although the gene(s) responsible for the phenotype is not known, perturbation of imprinted gene expression in human paternal uniparental disomy (pUPD) 14 and mouse (pUPD) 12 causes growth retardation and bone malformation (45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55).…”

Genomic imprinting of DIO3, a candidate gene for the syndrome associated with human uniparental disomy of chromosome 14

“…6 Patients with maternal or paternal UPD of human chromosome 14 (UPD14; named Temple and Kagami-Ogata syndromes, respectively) present with distinct developmental abnormalities, including hydrocephalus, hypotonia, abnormal growth, mental retardation, craniofacial dismorphisms, altered puberty onset, abnormal rib cage and others. 7,8 Several genes within this region, including DLK1 and MEG3, are subject to genomic imprinting, that is, they exhibit a high degree of monoallelic expression. 6 However, it is uncertain whether DIO3 is imprinted.…”

Novel deletions affecting the MEG3-DMR provide further evidence for a hierarchical regulation of imprinting in 14q32

“…[5][6][7][8] Genetic and epigenetic alterations affecting the imprinted gene cluster in 14q32 result in two different phenotypes currently known as maternal or paternal uniparental disomy 14 phenotypes (upd (14)mat, upd (14)pat). The upd (14)pat syndrome is characterized by polyhydramnios, a small bell-shaped thorax, facial dysmorphisms, abdominal wall defects, distal arthrogryposis and mental retardation, 9,10 whereas the upd(14)mat syndrome is characterized by pre and postnatal growth retardation, neonatal hypotonia, feeding problems and precocious puberty. [11][12][13] In both syndromes, three types of molecular alterations have been reported: uniparental disomy, deletions and epimutations.…”