Duplication 14(q24.3q31) in a father and daughter: Delineation of a possible imprinted region

Abstract

A number of clinical reports have described children with a variety of congenital anomalies in association with uniparental disomy (upd) of chromosome 14, suggesting that at least some genes on chromosome 14 are subject to parent of origin, or imprinting, effects. However, little else is known about this putative imprinting of chromosome 14. Both maternal and paternal upd have been observed, but a consistent phenotype has only been suggested for the former. Here we report on a child with developmental delay, microcephaly, distinct facial findings, and who has a duplication of 14q24.3q31. The same cytogenetic abnormality was found in her phenotypically normal father. We hypothesize that this segment of chromosome 14 contains maternally silenced genes, and that this duplicated segment defines an imprinted region on chromosome 14. Alternatively, this cytogenetic duplication may be unrelated to the girl's phenotypic anomalies, and this duplication may contain genes that are not subject to dosage effect.

Chromosome abnormalities without phenotypic consequences

“…Most of the Barber 2000Overhauser et al 1986Hand et al 2000Mascarello et al 1991Reddy 1999Batanian et al 2001Pelly et al 1992Davis et al 1999Barber et al 1991Li et al 2002Couturier et al 1985Hand et al 2000Witt et al 1988Rigola et al 2001 Duplication 1p21-p31 1q11-q22* 1q42.11-q42.12* 3q25-q25* 3q28-q29 4q31.3-q33* 5q15-q21* 6q24. Zaslav et al 1993Chan et al 2002Bortotto et al 1990Fryburg et al 1994Millard et al 1998Maltby et al 1999Li et al 1998Barber 2000Chan et al 2003Engelen et al 2000Harada et al 2002Stumm et al 2002Di Giacomo et al 2004Saxe et al 2003Robin et al 1997Cook et al 1997Wolff et al 1991 recorded cases are presented in Table 1 (after Barber). A chromosome 2 deletion involving the q13-q14.1 region, demonstrated by Sumption and Barber (2001), is a good example.…”

Allele-specific methylation of a functional CTCF binding site upstream of MEG3 in the human imprinted domain of 14q32

“…The abnormal phenotypes associated with UPD14 presumably result from the over-expression or under-expression of imprinted genes on this chromosome. Many studies have provided evidence that imprinted genes are located within the 14q24-q32 region (Robin et al 1997, Georgiades et al 1998. Subsequently, a cluster of imprinted genes including MEG3 and DLK1 was identified and localized to 14q32 (Kobayashi et al 2000, Miyoshi et al 2000, Schmidt et al 2000, Takada et al 2000, Wylie et al 2000, Charlier et al 2001a.…”

Mosaic monosomy 14: clinical features and recognizable facies

“…Three studies have sought to clarify the knowledge on imprinted regions on chromosome 14 (Robin et al, 1997;Georgiades et al, 1998;Sutton and Shaffer, 2000). Sutton and Shaffer (2000), in a comparison study of maternal and paternal UPD (Uniparental Disomy) 14 cases, with chromosome 14 deletion cases, in conjunction with Georgiades' 1998 study, and the knowledge of imprinted regions of mouse homologue (homologous to human chromosome 14) were able to conclude that 14q23-32 is a likely area where imprinted genes may reside.…”