Chromosomal imbalance letterArray-CGH detection of a de novo 0.8 Mb deletion in 19q13.32 associated with mental retardation, cardiac malformation, cleft lip and palate, hearing loss and multiple dysmorphic features
Section snippets
Methods of detection
High molecular weight genomic DNA was extracted from the patient's peripheral blood lymphocytes using the QIAamp DNA Blood Midi kit (Qiagen, Valencia, CA) according to the manufacturer's instructions. DNA concentration was determined with NanoDrop ND-1000 spectrophotometer and software (NanoDrop Technologies, Berlin, Germany). Detection of gene copy number was performed by array-Comparative Genomic Hybridization (CGH) experiments following standard and manufacturer's recommendations (Agilent™,
Chromosomal anomaly
Cytogenetic investigations, performed early after the patient's birth by conventional standard (400) or high-resolution (800) R-banding pattern on 30 metaphases or prometaphases from peripheral lymphocytes cultured under phytohemagglutinin-stimulation, revealed a normal 46,XX karyotype. Fluorescence in situ hybridization (FISH) experiments performed on prometaphase preparations by using a set of 41 subtelomeric probes (Chromoprobe Multiprobe T system, Cytocell, Cambridge, UK) did not detect any
Method of confirmation
FISH experiments were performed using a BAC clone on metaphase cells. The deletion was confirmed by using a CTC-483I11 probe whose genomic position, extending from 52 341 333 to 52 496 454 bp, is located inside the deletion interval (Fig. 1B). The DNA probe was labeled by nick translation procedure with spectrum green-dUTP using a commercial kit (Vysis, Downers Grove, IL). Chromosomes were counterstained with 4′-6-diamino-2-phenyl-indole (DAPI). Hybridized cells were analyzed with a Zeiss
Causative of the phenotype
Analysis of the parents' peripheral lymphocyte methaphases did not reveal any chromosome deletion by FISH analyses while using the same fluorescent BAC clone. This finding indicates that the deletion found in the patient was de novo.
Clinical description
The Caucasian patient is the second child of healthy nonconsanguineous 31 years old G3P2 mother and 32 years old father. Her older brother is healthy. The patient was born at term (39 weeks) after an uncomplicated pregnancy, except for a threatening miscarriage at 10 weeks. At birth, the patient's weight, length and head circumference were 3250 g (50th centile), 51 cm (75th centile), 35 cm (75th centile) respectively; Apgar was 8/8 (1/5 min). Immediately after birth, the child was referred to the
Discussion
Deletion of chromosome 19 is quite uncommon and, for the best of our knowledge, only four cases of interstitial deletion involving 19q have been reported [1], [2]. Three cases of cryptic deletion at 19q13.2 have been identified by a Swedish group by means of microsatellite or FISH analyses in children with Diamond-Blackfan anemia, a constitutive red blood cell hypoplasia (for review see Gustavsson et al., 1998 [1]). A new microdeletion syndrome has then been suggested [1]. An additional
Acknowledgements
We thank Delphine Ceraso, Alexis Leurent, Caroline Thuilliez for their excellent technical assistance.
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Copy number variation analysis of patients with intellectual disability from North-West Spain
2017, GeneCitation Excerpt :These authors defined a new 19q13.32 microdeletion syndrome and suggested that the phenotypic severity depends on the size and gene content of the CNV. In fact, Patient 1 and the patient reported by Leal et al. (2009), both with large de novo deletions, shared a recurrent syndromic phenotype, including ID, facial asymmetry, oculomotor paralysis, ptosis, cleft lip and palate, micrognathia, kyphoscoliosis and congenital cardiac and intestinal defects; however, their Patients 2 and 3 did not present most of the distinctive features, probably because they carried shorter deletions, not including the entire critical region for this syndrome. They also suggested that the haploinsufficiency of some of the genes deleted in their patients could explain their phenotypes; specifically, they highlighted NPAS1, NAPA, ARHGAP35, SLC8A2, DHX34, MEIS3 and ZNF541, due to their expression in the brain parenchyma, glia, heart, gastrointestinal tract and musculoskeletal system (Castillo et al. 2014).
19q13.32 microdeletion syndrome: Three new cases
2014, European Journal of Medical GeneticsCitation Excerpt :In conclusion, we present and compare three unrelated patients (Fig. 2 and Table 1) with a deletion involving chromosome 19q13.32, whose phenotypic severity depends on the size and content of the deletion. A recognizable deletion syndrome is defined by the shared phenotypic features in the patient reported by Leal et al. [2009] and our Patient 1. They both share a deleted region (minimally, 52,035,320–52,758,151; maximally 51,970,589–52,878,649), where the commonly deleted 20–23 candidate genes are expressed in the brain parenchyma, glia, heart, gastrointestinal tract and musculoskeletal system and likely play a fundamental role in the expression of this phenotype.
A microduplication of 5p15.33 reveals CLPTM1L as a candidate gene for cleft lip and palate
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