Description: SDHD (succinate-ubiquinone oxidoreductase subunit D, a mitochondrial complex II gene) showed
paternal expression in four glomus tumours (nonchromaffin paragangliomas), in the absence of
apparent loss of heterozygosity (Badenhop RF et al, 2001), but biallelic expression in lymphocytes, 2 adult brain, 3 fetal
brains and 1 fetal kidney (Badenhop RF et al, 2001; Baysal
BE et al, 2000).
Mutations of SDHD cause hereditary paraganglioma type 1 (glomus tumours) which are always
inherited from carrier fathers (Baysal
BE et al, 1997; Mariman
EC et al, 1995; van
der Mey AG et al, 1989; Milunsky
J et al, 1997).
Hensen
EF et al, 2004 showed deletion of the entire maternal chromosome 11 in all nineteen cases of
paraganglioma,
and suggest that the apparent imprinting of SDHD is attributable to the need to delete both a maternally
expressed tumour suppressor gene elsewhere on chromosome 11 (eg, 11p15), and the wildtype copy of
SDHD. Yeap PM et al (2011) confirmed that
tumour formation requires the loss of both the wild-type SDHD allele and maternal 11p15, leading to
the predominant but not exclusive pattern of disease inheritance after paternal SDHD transmission.
Margetts CD et al, 2005 found loss of
the maternal allele in VHL-associated (n = 3) and sporadic phaeochromocytomas (n = 7) without SDHD
mutations, suggesting that 11p loss reflects the involvement of other imprinted 11p15.5 genes and
providing evidence against imprinting of SDHD itself.
Baysal et al, (2011) claim evidence for
imprinting at a non-coding gene, termed UPGL (Untranslated in ParaGanglioma Locus) situated 206 kb
telomeric to the SDHD locus. They report allele specific methylation in the adrenal cortex of four
out of five fetuses. In one sample the more methylated allele was identified as maternal. Allelic
expression imbalance for UPGL was detected in one of seven fetuses; the other six showed biallelic
expression.
Morcos L et al, (2011) found no evidence of
allelic expression bias in lymphoblast cell lines.
Baran Y et al (2015) found no evidence of
imprinting of SDHD in multiple adult tissues (using RNA-seq). |