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DELETION (1)(P32.2–P32.3) DETECTED BY ARRAY-CGH IN A PATIENT WITH DEVELOPMENTAL DELAY/MENTAL RETARDATION, DYSMORPHIC FEATURES AND LOW CHOLESTEROL: A NEW MICRODELETION SYNDROME?
Global Developmental Delay
Oligonucleotide aCGH
Submicroscopic Chromosome Deletion 1p32
Low Serum Cholesterol
Author
Affilliation
Universidade Federal do Rio de Janeiro. Rio de Janeiro, RJ, Brasil / UCLA. David Geffen School of Medicine. Department of Pathology and Lab Medicine. Los Angeles, California.
Universidade Federal do Rio de Janeiro. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Rio de Janeiro, RJ, Brasil.
Rikshospitalet-Radiumhospitalet Medical Center. Department of Medical Genetics. Medical Genetics Laboratory. Oslo, Norway.
UCLA. David Geffen School of Medicine. Department of Pathology and Lab Medicine. Los Angeles, California.
UCLA. David Geffen School of Medicine. Department of Pathology and Lab Medicine. Los Angeles, California.
Universidade Federal do Rio de Janeiro. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Rio de Janeiro, RJ, Brasil.
Rikshospitalet-Radiumhospitalet Medical Center. Department of Medical Genetics. Medical Genetics Laboratory. Oslo, Norway.
UCLA. David Geffen School of Medicine. Department of Pathology and Lab Medicine. Los Angeles, California.
UCLA. David Geffen School of Medicine. Department of Pathology and Lab Medicine. Los Angeles, California.
Abstract
We report on a 25-year-old male with mental retardation and
global developmental delay, low levels of total and LDL
cholesterol and dysmorphism, which includes macroce-phaly, hypertelorism, synophrys, telecanthus, prominent
philtrum, low set ears, bilateral cataracts, bilateral cleft lip
with cleft palate and widely spaced nipples. While his
karyotype and subtelomeric FISH studies were normal, a de
novo, 5.4 Mb interstitial deletion at 1p32 [del(1)(p32.2–
p32.3)] was identified by oligonucleotide aCGH. The deleted
region encompasses a cluster of genes involved in fatty acid
oxidation and cholesterol metabolism. One of these genes is
PCSK9, a key regulator for a number of cell-surface LDL
receptors. In addition to the loss of the paternal allele, our
patient is hemizygous for the A443T weak loss-of-function
mutation in exon 8 ofPCSK9. Loss-of-function mutations
withinPCSK9have been shown to cause hypocholester-olemia. Another gene also mapped to this region and deleted
in this patient is DAB1, reported to be involved in brain
development. Based on the findings in the current patient
and in the four previously reported individuals with
del(1)(p32.2–p32.3), we suggest that these patients may
have a new microdeletion syndrome that may have gone
undetected because of its location in a G-negative band.
However, the condition can easily be identified by array-CGH.
Keywords
Mental RetardationGlobal Developmental Delay
Oligonucleotide aCGH
Submicroscopic Chromosome Deletion 1p32
Low Serum Cholesterol
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