De novo 16p13.11 microdeletion identified by high‐resolution array CGH in a fetus with increased nuchal translucency

Abstract

Objective We investigated the application of high‐resolution microarray‐based comparative genomic hybridisation (array CGH) on a fetus showing increased nuchal translucency (NT).Design Case study.Setting Tertiary referral obstetrics unit.Sample Pregnant woman attended the antenatal clinic.Methods Conventional karyotyping and genetic test was carried out for the alpha‐globin gene. High‐resolution array CGH using the high‐density 244K Agilent microarray was performed on fetal blood sample by cordocentesis to investigate the possibility of any genomic imbalance.Main outcome measures Detection of chromosomal abnormality.Results Karyotyping analysis showed 46,XY. Molecular genetic diagnosis confirms the fetus has Hb‐H constant spring disease but cannot explain the increased NT to 3.2 mm. Array CGH analysis discovered a 1.32‐Mb microdeletion on chromosome 16p13.11. Deletion at 16p13.11 has been implicated to predispose to autism and/or mental retardation. Baby was delivered at 40 weeks of gestation, and follow up was carried out at 3 months of age without sign of mental retardation/developmental delay.Conclusions This case study demonstrated that array CGH can accurately calibrate the size and identify de novo interstitial chromosome imbalances. However, the presence of chromosome copy variants with unknown clinical significance currently limits its wider scale application in prenatal diagnosis and needs further investigations.

Increased nuchal translucency in euploid fetuses—what should we be telling the parents?

“…Additional genetic investigations in fetuses with enlarged NT and normal conventional karyotype, such as molecular testing (subtelomere MLPA and CGH microarrays) are promising techniques for identifying microscopic genomic aberrations (microdeletions, unbalanced translocations) responsible for syndromic associations including structural anomalies and mental retardation (Lespinasse et al, 2004;Chen et al, 2005;Farina et al, 2006;Law et al, 2008). However, as their value has not yet been investigated prospectively in large series, caution should be used in interpreting isolated findings in fetuses without structural anomalies.…”

16p13.11 duplication is a risk factor for a wide spectrum of neuropsychiatric disorders

“…[4][5][6][7][8][9] One of them is the 16p13.11 microdeletion syndrome characterized by developmental delay/intellectual disabilities (DD/ID) with or without multiple congenital abnormalities. [6][7][8]10,11 Although 16p13.11 microduplication was initially considered to be a rare benign variant, 6 accumulated evidence indicates that this duplication is enriched in patients with autism, 8 unexplained ID, 10 schizophrenia, 12 epilepsy, 13 and attentiondeficit hyperactivity disorder. 14 Since 2008, we have evaluated 1645 consecutive pediatric patients by microarray-based comparative genomic hybridization (aCGH) technique using the Agilent Human Genome Microarray Kit 244K platform according to the described protocol.…”

Clinical utility gene card for: 16p13.11 microdeletion syndrome

“…The 16p13.11 microdeletions are pleiotropic genomic variants with broad phenotypic manifestations, including neurodevelopmental phenotypes such as autism, mental retardation, epilepsy and learning difficulties and non-CNS phenotypes such as physical dysmorphisms and congenital anomalies. [2][3][4][5][6][7][8][9][10][11][12] This variable phenotypic expressivity represents a challenge for clinical diagnosis because similar clinical features have been associated with a number of other genomic variations (eg, del1q21.1 or del15q11.2), and a characteristic common phenotype for the 16p13.11 microdeletion carriers has not yet been identified. Furthermore, clinical diagnosis can also be hampered by the presence of 'second-hits', additional pathogenic variations in other genomic regions that act in concert with the 16p13.11 microdeletions, and are able to exacerbate or mask some of their phenotypic symptoms.…”

“…[2][3][4][5][6][7][8][9][10][11][12] Interval II (chr16:15.48-16.32 Mb, GRCh37/hg19) represents the critical region of the genomic variation, being contained in the great majority of the 16p13.11 microdeletions identified so far. [2][3][4][5][6][7][8][9][10][11][12] It encompasses a core set of eight protein-coding genes, including NDE1, the strongest candidate gene for the neurodevelopmental phenotypes associated with the 16p13.11 microdeletions. NDE1 encodes the nuclear distribution protein nudE homolog 1, a centrosomal protein that has a crucial role in the process of mammalian encephalisation and human cerebral cortex growth.…”