Maternal heterodisomy and isodisomy (>28 cases in literature) is associated with a characteristic
similar to that of Prader-Willi syndrome (hypotonia, motor developmental delay, mild dysmorphic
facial features, low birth weight, growth abnormalities (precocious puberty) (Kamnasaran
D et al. 2001; Ledbetter
DH et al. 1995; Hurst
LD et al. 1997; Tomkins
DJ et al. 1996; Kotzot
D, 2007; Kagami
M et al, 2008; Ogata T et al, 2008; Aretz S et al, 2005; Hosoki K et al, 2009).
Paternal isodisomy or heterodisomy of
chromosome 14 (at least 17 cases) is associated with severe mental and musculoskeletal phenotype (Stevenson
DA et al, 2004; Kurosawa
K et al. 2002; Kamnasaran
D et al. 2001; Walter
CA et al. 1996; Cotter
PD et al. 1997; Ogata T et al, 2008) which is recapitulated in paternal UPD of mouse chromosome 12.
Analysis of UPD14 cases suggests that imprinted genes on 14q32 are responsible for
the phenotypes, but also that other imprinted regions on chr14 may exist (Kotzot
D et al. 2001
for a review see Kotzot et al 2004; Sutton
VR et al. 2000).
A patient with clinical features of maternal UPD14,
including growth retardation, hypotonia, scoliosis, small hands
and feet, and advanced puberty, had loss of methylation
of the IG-DMR but no evidence of maternal UPD14 (Temple
IK et al, 2007). This case
suggests that the maternal UPD14
phenotype is due to aberrant gene expression within the
imprinted domain at 14q32.
Quantitative real-time PCR showed that RTL1 expression level was about five times higher in the
placental samples of two patients with paternal uniparental disomy 14 compared to controls,
consistent with paternal expression (Kagami M et al, 2012).