Small 7p22.3 microdeletion: Case report of Snx8 haploinsufficiency and neurological findings.

Some cases of chromosome 7p22.3 deletions have been reported, but the genotype-phenotype correlation is still uncertain. Neurodevelopmental delay and heart anomalies have been recorded as the most recurrent defects. We describe the clinical features of a four-year-old male child with a 139 kb deletion at 7p22.3 involving SNX8 gene, inherited from a mosaic mother. The same deletion is also present in the fetus on the ongoing third pregnancy of the couple with normal fetal ultrasound assessment. The proband was prenatally diagnosed with left kidney agenesis. He does not show any congenital heart disease, but mild intellectual disability, learning and language delay, and severe behavioral problems related to the hyperactive-impulsive and inattentive area. These clinical features are also evident in other 7p22 deletions cases involving the SNX8 gene, supporting the role of this gene in neurodevelopment. Conversely, the revision of all published cases with small 7p22 deletions and the absence of heart malformations in the present family confirm that this region is involved in heart development, anyway did not confirm the role of SNX8 in cardiac phenotypes, either due to the reduced penetrance or the involvement of other candidate genes.

Clinical Correlates of Autosomal Chromosomal Abnormalities in an Electronic Medical Record-Linked Genome-Wide Association Study: A Case Series.

Although mosaic autosomal chromosomal abnormalities are being increasingly detected as part of high-density genotyping studies, the clinical correlates are unclear. From an electronic medical record (EMR)-based genome-wide association study (GWAS) of peripheral arterial disease, log-R-ratio and B-allele-frequency data were used to identify mosaic autosomal chromosomal abnormalities including copy number variation and loss of heterozygosity. The EMRs of patients with chromosomal abnormalities and those without chromosomal abnormalities were reviewed to compare clinical characteristics. Among 3336 study participants, 0.75% (n = 25, mean age = 74.8 ± 10.7 years, 64% men) had abnormal intensity plots indicative of autosomal chromosomal abnormalities. A hematologic malignancy was present in 8 patients (32%), of whom 4 also had a solid organ malignancy while 2 patients had a solid organ malignancy only. In 50 age- and sex-matched participants without chromosomal abnormalities, there was a lower rate of hematologic malignancies (2% vs 32%, P < .001) but not solid organ malignancies (20% vs 24%, P = .69). We also report the clinical characteristics of each patient with the observed chromosomal abnormalities. Interestingly, among 5 patients with 20q deletions, 4 had a myeloproliferative disorder while all 3 men in this group had prostate cancer. In summary, in a GWAS of 3336 adults, 0.75% had autosomal chromosomal abnormalities and nearly a third of them had hematologic malignancies. A potential novel association between 20q deletions, myeloproliferative disorders, and prostate cancer was also noted.

Clinical Correlates of Autosomal Chromosomal Abnormalities in an Electronic Medical Record-Linked Genome-Wide Association Study: A Case Series.

Although mosaic autosomal chromosomal abnormalities are being increasingly detected as part of high-density genotyping studies, the clinical correlates are unclear. From an electronic medical record (EMR)-based genome-wide association study (GWAS) of peripheral arterial disease, log-R-ratio and B-allele-frequency data were used to identify mosaic autosomal chromosomal abnormalities including copy number variation and loss of heterozygosity. The EMRs of patients with chromosomal abnormalities and those without chromosomal abnormalities were reviewed to compare clinical characteristics. Among 3336 study participants, 0.75% (n = 25, mean age = 74.8 ± 10.7 years, 64% men) had abnormal intensity plots indicative of autosomal chromosomal abnormalities. A hematologic malignancy was present in 8 patients (32%), of whom 4 also had a solid organ malignancy while 2 patients had a solid organ malignancy only. In 50 age- and sex-matched participants without chromosomal abnormalities, there was a lower rate of hematologic malignancies (2% vs 32%, P < .001) but not solid organ malignancies (20% vs 24%, P = .69). We also report the clinical characteristics of each patient with the observed chromosomal abnormalities. Interestingly, among 5 patients with 20q deletions, 4 had a myeloproliferative disorder while all 3 men in this group had prostate cancer. In summary, in a GWAS of 3336 adults, 0.75% had autosomal chromosomal abnormalities and nearly a third of them had hematologic malignancies. A potential novel association between 20q deletions, myeloproliferative disorders, and prostate cancer was also noted.