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?
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 macrocephaly, 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 of PCSK9. Loss-of-function mutations within PCSK9 have been shown to cause hypocholesterolemia. 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.
Mulatinho
Milene
M
Universidade Federal do Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil.
Llerena
Juan
J
Leren
Trond P
TP
Rao
P Nagesh
PN
Quintero-Rivera
Fabiola
F
D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D002675:Child, Preschool; D002784:Cholesterol / Q000097:blood / Q000235:genetics*; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000235:genetics; D002658:Developmental Disabilities / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D007621:Karyotyping; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases / Q000235:genetics; D013577:Syndrome
D002784:Cholesterol; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases