Genomic detection of a familial 382 Kb 6q27 deletion in a fetus with isolated severe ventriculomegaly and her affected mother.

Terminal deletions of the chromosome 6q27 region are rare genomic abnormalities, linked to specific brain malformations and other neurological phenotypes. Reported cases have variable sized genomic deletions that harbor several genes including the DLL1 and TBP. We report on an inherited 0.38 Mb terminal deletion of chromosome 6q27 in a 22-week fetus with isolated bilateral ventriculomegaly and her affected mother using microarray-based comparative genomic hybridization and fluorescent in situ hybridization (FISH). The deleted region harbors at least seven genes including DLL1 and TBP. The affected mother had a history of hydrocephalus, developmental delay, and seizures commonly associated with DLL1 and TBP 6q27 deletions. This deletion is one of the smallest reported isolated 6q27 terminal deletions. Our data provides additional evidence that haploinsufficiency of the DLL1 and TBP genes may be sufficient to cause the ventriculomegaly, seizures, and developmental delays associated with terminal 6q27 deletions, indicating a plausible role in the abnormal development of the central nervous system.

Compound heterozygous microdeletion of chromosome 15q13.3 region in a child with hypotonia, impaired vision, and global developmental delay.

Homozygous or compound heterozygous microdeletion of 15q13.3 region is a rare but clinically recognizable syndrome manifested by profound intellectual disability, muscular hypotonia, intractable seizures, and visual impairment. We identified a compound heterozygous 15q13.3 microdeletion in a 23-month-old girl with global developmental delay, generalized muscular hypotonia, and visual dysfunction. The larger deletion was approximately 1.28 Mb in size and contained seven genes including the TRPM1 and CHRNA7, while the smaller deletion was estimated to be 410 Kb in size and contained only CHRNA7. Compound heterozygous 15q13.3 microdeletion is extremely rare and to the best of our knowledge only two such patients have been reported in literature thus far. The findings in our patient suggest that the pathogenesis of visual dysfunction, which is a consistent finding in homozygous/compound heterozygous 15q13.3 microdeletion depends upon the size of microdeletion. Homozygous loss of TRPM1 likely causes retinal dysfunction while homozygous loss of CHRNA7 alone may lead to visual impairment by cortical mechanisms.