TY - JOUR
T1 - Refinement of causative genes in monosomy 1p36 through clinical and molecular cytogenetic characterization of small interstitial deletions
AU - Rosenfeld, Jill A.
AU - Crolla, John A.
AU - Tomkins, Susan
AU - Bader, Patricia
AU - Morrow, Bernice
AU - Gorski, Jerome
AU - Troxell, Robin
AU - Forster-Gibson, Cynthia
AU - Cilliers, Deirdre
AU - Hislop, R. Gordon
AU - Lamb, Allen
AU - Torchia, Beth
AU - Ballif, Blake C.
AU - Shaffer, Lisa G.
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/8
Y1 - 2010/8
N2 - Monosomy 1p36 is the most common terminal deletion syndrome seen in humans, occurring in ∼1 in 5,000 live births. Common features include mental retardation, characteristic dysmorphic features, hypotonia, seizures, hearing loss, heart defects, cardiomyopathy, and behavior abnormalities. Similar phenotypes are seen among patients with a variety of deletion sizes, including terminal and interstitial deletions, complex rearrangements, and unbalanced translocations. Consequently, critical regions harboring causative genes for each of these features have been difficult to identify. Here we report on five individuals with 200-823 kb overlapping deletions of proximal 1p36.33, four of which are apparently de novo. They present with features of monosomy 1p36, including developmental delay and mental retardation, dysmorphic features, hypotonia, behavioral abnormalities including hyperphagia, and seizures. The smallest region of deletion overlap is 174 kb and contains five genes; these genes are likely candidates for some of the phenotypic features in monosomy 1p36. Other genes deleted in a subset of the patients likely play a contributory role in the phenotypes, including GABRD and seizures, PRKCZ and neurologic features, and SKI and dysmorphic and neurologic features. Characterization of small deletions is important for narrowing critical intervals and for the identification of causative or candidate genes for features of monosomy 1p36 syndrome.
AB - Monosomy 1p36 is the most common terminal deletion syndrome seen in humans, occurring in ∼1 in 5,000 live births. Common features include mental retardation, characteristic dysmorphic features, hypotonia, seizures, hearing loss, heart defects, cardiomyopathy, and behavior abnormalities. Similar phenotypes are seen among patients with a variety of deletion sizes, including terminal and interstitial deletions, complex rearrangements, and unbalanced translocations. Consequently, critical regions harboring causative genes for each of these features have been difficult to identify. Here we report on five individuals with 200-823 kb overlapping deletions of proximal 1p36.33, four of which are apparently de novo. They present with features of monosomy 1p36, including developmental delay and mental retardation, dysmorphic features, hypotonia, behavioral abnormalities including hyperphagia, and seizures. The smallest region of deletion overlap is 174 kb and contains five genes; these genes are likely candidates for some of the phenotypic features in monosomy 1p36. Other genes deleted in a subset of the patients likely play a contributory role in the phenotypes, including GABRD and seizures, PRKCZ and neurologic features, and SKI and dysmorphic and neurologic features. Characterization of small deletions is important for narrowing critical intervals and for the identification of causative or candidate genes for features of monosomy 1p36 syndrome.
KW - 1p36
KW - GABRD
KW - Interstitial deletion
KW - Monosomy
KW - PRKCZ
KW - SKI
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U2 - 10.1002/ajmg.a.33516
DO - 10.1002/ajmg.a.33516
M3 - Article
C2 - 20635359
AN - SCOPUS:77955286349
SN - 1552-4825
VL - 152
SP - 1951
EP - 1959
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 8
ER -