On The Spot e-News

Volume 5, Issue 10 | December 2010

In this issue:

Researchers report evidence of germline mosaicism in a recurrent interstitial 1p36 deletion

Researchers recently reported the first example of apparent familial recurrence involving an interstitial deletion resulting in monosomy 1p36.

Monosomy 1p36 is the most commonly observed subtelomeric deletion syndrome, clinical features of which include characteristic dysmorphic facial features, intellectual disability, growth impairment, hearing impairment, seizures, and heart defects.

The mode of inheritance for monosomy 1p36 is primarily sporadic, and, other than deletions arising from malsegregation of a balanced parental translocation, familial deletions have not been described. In their study, published in the American Journal of Medical Genetics, investigators from Signature Genomics, Children's Hospital of Philadelphia, and the Polish Academy of Sciences identified by microarray analysis identical interstitial deletions at 1p36 in two siblings who display mild manifestations of monosomy 1p36, including hearing loss and left ventricular non-compaction. The parent of origin of the deletion for both children was the same, suggestive of germline mosaicism as the mechanism of recurrence.

These results reinforce that the risk of germline mosaicism should be discussed when counseling families with a new diagnosis in a child with monosomy 1p36.

In addition, because the deletion was small and interstitial, it was not detectable by subtelomere FISH; coupled with the presence of mild features in the siblings, these results underscore the utility of aCGH for diagnosing chromosome abnormalities. The presence of hearing loss and left ventricular non-compaction in these siblings also narrows the region in which to search for causative genes of these features.

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Happy Holidays from Signature Genomics

Although it can be said many ways, the sentiment is universal.
Happy holidays, best wishes and good health in 2011.

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