Monosomy 1p36 Syndrome Resource Page
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Contact Information
Dr. Lisa G. Shaffer, Ph.D.
Professor
Washington State University Spokane
Health Research and Education
Center
Box 1495
Spokane, WA 99210-1495
Ph: (509) 368-6710
Fax: (509) 358-7627
E-mail:
lshaffer@wsu.edu
Laboratory Supervisor
Caron Glotzbach
Genetics Research Tech
Washington State University Spokane
Health Research and Education
Center
Box 1495
Spokane, WA 99210-1495
Ph: (509) 368-6711
Fax: (509) 358-7627
E-mail:
glotzbach@wsu.edu |
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Caused by a terminal deletion of the most distal
band of the short arm of chromosome 1, monosomy 1p36 is the most commonly
observed terminal chromosomal deletion, occurring in approximately 1 in
5,000 births (Shaffer and Lupski 2000;
Heilstedt et al. 2003b). As first described
by the Shaffer lab in 13 subjects (Shapira et al.
1997), craniofacial characteristics of this contiguous gene deletion
syndrome (CGDS)--so-called because it involves the deletion of multiple
adjacent genes on the same chromosome arm--include late-closing, large anterior
fontanels (membranous intervals at the intersection of the cranial bones
at the crown of the skull), brachycephaly (disproportionate shortness of
the head), deep-set eyes, flat nasal bridge, asymmetric ears, and pointed
chin. Monosomy 1p36 is also associated with mental retardation,
developmental delay, hearing impairment, seizures, growth impairment, and
heart defects (Shapira et al. 1997;
Slavotinek et al. 1999;
Heilstedt et al. 2003a). Over 90 subjects
with rearrangements of 1p36 have enrolled in our studies, of which 61 were
recently published (Heilstedt et al. 2003a).
The deletion sizes in the subjects vary considerably (Wu
et al. 1999; Heilstedt et al. 2003a);
however, there is some uniformity in the origin of the deletions, with
over 60% being maternally derived (Wu et al. 1999;
Heilstedt et al. 2003a). Candidate genes have been proposed for
some of the individual features of monosomy 1p36, including seizures (Heilstedt
et al. 2001) and facial clefting anomalies (Colmenares
et al. 2002).
The Shaffer laboratory has recently identified
possible mechanisms for the generation and/or stabilization of terminal
deletions of 1p (Ballif et al. 2003;
Ballif et al. 2004a;
Ballif et al. 2004b; Gajecka et al. 2005). In addition, the Shaffer laboratory has recently
demonstrated the use of microarrays--a rapid, sensitive, and
high-resolution technology for the detection of many chromosomal
anomalies--in the detection of deletions of 1p36 (Yu et
al. 2003).
For more information, please see the contact
information to the right.
REFERENCES
Click on the links below to access these
articles. If you are unable to read these documents, please download the
free Adobe
Acrobat reader.
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Ballif BC, Yu W, Shaw CA, Kashork CD, Shaffer LG (2003) Monosomy
1p36 breakpoints suggest pre-meiotic breakage-fusion-bridge cycles are
involved in generating terminal deletions. Hum Mol Genet 12:2153-2165.
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Ballif BC, Wakui K, Gajecka M, Shaffer LG (2004a) Translocation
breakpoint mapping and sequence analysis in three monosomy 1p36 subjects
with der(1)t(1;1)(p36;q44) suggest mechanisms for telomere capture in
stabilizing de novo terminal rearrangements. Hum Genet 114:198-206.
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Ballif BC,
Gajecka M, Shaffer LG (2004b) Monosomy
1p36 breakpoints indicate repetitive DNA sequence elements may be
involved in generating and/or stabilizing some terminal deletions.
Chromosome Res 12:133-141.
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Colmenares C, Heilstedt HA, Shaffer LG, Schwartz S, Berk
M, Murray JC, Stavnezer E (2002) Loss of the
SKI proto-oncogene in individuals affected with 1p36 deletion syndrome
is predicted by strain-dependent defects in Ski-/- mice. Nat Genet
30:106-109.
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Gajecka M, Yu W, Ballif BC, Glotzbach CD, Bailey KA, Shaw CA, Kashork
CD, Heilstedt HA, Ansel DA, Theisen A, Rice R, Rice DP, Shaffer LG
(2005) Delineation of mechanisms and regions of dosage imbalance in
complex rearrangements of 1p36 leads to a putative gene for regulation
of cranial suture closure. Eur J Hum Genet 13:139-149.
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Heilstedt HA,
Burgess DL, Anderson AE, Chedrawi A, Tharp B, Lee O, Kashork CD, Starkey
DE, Wu YQ, Noebels JL, et al. (2001) Loss of the potassium channel
beta-subunit gene, KCNAB2, is associated with epilepsy in patients with
1p36 deletion syndrome. Epilepsia 42:1103-1111.
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Heilstedt HA, Ballif BC, Howard LA, Lewis RA, Stal S, Kashork CD, Bacino
CA, Shapira SK, Shaffer LG (2003a) Physical map of 1p36, placement
of breakpoints in monosomy 1p36, and clinical characterization of the
syndrome. Am J Hum Genet 72:1200-1212.
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Heilstedt HA, Ballif BC, Howard LA, Kashork
CD, Shaffer LG (2003b) Population data suggest that deletions of 1p36
are a relatively common chromosome abnormality. Clin Genet 64:310-316.
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Shaffer LG, Lupski JR (2000) Molecular mechanisms for constitutional
chromosomal rearrangements in humans. Annu Rev Genet 34:297-329.
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Shapira SK, McCaskill C, Northrup H, Spikes AS, Elder FF, Sutton VR,
Korenberg JR, Greenberg F, Shaffer LG (1997) Chromosome 1p36 deletions:
the clinical phenotype and molecular characterization of a common newly
delineated syndrome. Am J Hum Genet 61:642-650.
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Slavotinek A, Shaffer LG, Shapira SK (1999) Monosomy 1p36. J Med
Genet 36:657-663.
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Wu YQ, Heilstedt HA, Bedell JA, May KM, Starkey DE, McPherson JD,
Shapira SK, Shaffer LG (1999) Molecular refinement of the 1p36
deletion syndrome reveals size diversity and a preponderance of
maternally derived deletions. Hum Mol Genet 8:313-321.
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Yu W, Ballif BC, Kashork CD, Heilstedt HA, Shaw CA, Shaffer, LG (2003)
Development of a comparative genomic hybridization microarray and
demonstration of its utility with 25 well-characterized human 1p36
deletions. Hum Mol Genet 12:2145-2152.
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