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?

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 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.

The exon junction complex component Magoh controls brain size by regulating neural stem cell division

“…Of note, MAGOH is found within a 55-gene deletion on 1p32.3 associated with mental retardation and brain size abnormalities31. In addition, RBM8A is one of 15 genes in a 0.4 Mb microdeletion on 1q21.1 associated with microcephaly32,33.…”

Genomic approaches for studying craniofacial disorders

“…These arrays offer a good genome‐wide coverage with millions of SNPs and CNV probes. With these arrays, microdeletions and microduplications of a length as small as a few hundred base pairs have been detected in studies of syndromic forms of CL/P [Mulatinho et al, ; Petrin et al, ; Barber et al, ; Izzo et al, ]. One example of using oligoarrays is shown by Izzo et al [].…”

Systematic analysis of copy number variants of a large cohort of orofacial cleft patients identifies candidate genes for orofacial clefts

“…Large structural alterations of the genome, including deletions and duplications of genomic regions termed copy number variations (CNVs), have been studied in OFC patients using classical genetic analyses such as FISH, CGH arrays or, more recently, SNP arrays (FitzPatrick et al 2003 ; Mulatinho et al 2008 ; Barber et al 2013 ; Izzo et al 2013 ). Some of the identified genes including SUMO 1, CLPTM1L and BMP2 have also been validated in animal models (Shi et al 2009 ; Sahoo et al 2011 ; Williams et al 2012 ).…”