SNP Array Clinical Report
Results
Fetus is female with a loss of 5.7 Mb at 1q43-q44, from nucleotide 243,206,626 to 248,928,328, encompassing 95 genes.
Fetus also has a gain of 45.9 Mb at 4q31.21-q35.2, from nucleotide 144,135,967 to 190,016,707, encompassing 236 genes.
Chromosome 1q43-q44 deletion syndrome is characterized by moderate to severely impaired intellectual development, limited or absent speech, and variable but characteristic facial features — including a round face, prominent forehead, flat nasal bridge, hypertelorism, epicanthal folds, and low-set ears. Additional features may include hypotonia, poor growth, microcephaly, agenesis of the corpus callosum, and seizures. The phenotype is variable, and not all features are observed in all patients, which may reflect incomplete penetrance or variable expressivity. (PMID: 2180092)
Distal trisomy 4q is a rare chromosomal anomaly resulting from partial duplication of the long arm of chromosome 4, with a highly variable phenotype typically characterized by psychomotor delay, intellectual disability, and craniofacial dysmorphism.
| Coordinate* | Type of Imbalance | Size | Classification** |
|---|---|---|---|
| arr[hg38] 1q43-q44(243206626_248928328)×1 | Loss (1 copy) | 5.7 Mb | Pathogenic |
| arr[hg38] 4q31.21-q35.2(144135967_190016707)×3 | Gain (3 copies) | 45.9 Mb | Pathogenic |
*Based on ISCN (2020). **Per American College of Medical Genetics (ACMG) standards and guidelines for interpretation and reporting of postnatal constitutional copy number variants, Genetics in Medicine, 2011.
Recommendations
Parental chromosome examination is recommended to determine the origin of the detected copy number variants (de novo vs. inherited, including possible parental balanced rearrangement). Genetic counseling is recommended to discuss recurrence risk and clinical implications for the family.
Method
- Technique: Single Nucleotide Polymorphism (SNP) array — high-throughput genotyping.
- Platform: Infinium Global Screening Array-24 v3.0 BeadChip, run on the Illumina iScan™ platform.
- Marker Count: 654,027 genetic markers.
- Reference Genome: NCBI Human Genome Build 38 (GRCh38).
- Analysis Software: GenomeStudio.
- Variant Databases: DECIPHER, DGV, ClinVar, and gnomAD SV.
- Reporting Policy: Variants classified as benign or likely benign, and copy number variants without OMIM genes or found in the Database of Genomic Variants, are not reported. The CNV location is reported by region and location on the chromosome, and includes the min/max size of the span of loss or gain. Minimum size (kb/Mb) represents the distance between the first deviated proximal and last deviated distal probes of the CNV. Maximum size (kb/Mb) represents the distance between the first non-deviated proximal and distal probes flanking the CNV, and genomic coordinates are reported based on the combination of the deviated copy number and SNP probes at the CNV boundaries.
Limitations
- This technique will not detect balanced rearrangements, point mutations, or low-level mosaicism.
- Aberrations on the Y chromosome and in the pseudoautosomal region (PAR) cannot be detected with high accuracy.
- The integration site of duplications cannot be determined by this technique.
- While the GSA v3.0 provides comprehensive coverage of common and rare variants, it may not capture all possible genetic variation.
- Deletions smaller than 0.5 Mb and duplications smaller than 1 Mb may not be reliably detected.