Congenital Hydrocephalus and Hemivertebrae Associated with De Novo Partial Monosomy 6q (6q25.3 ~>qter)

2015-12-31 00:00:18

Balkan Journal of Medical Genetics; 18(1)2015: 77-84; DOI: 10.1515/bjmg-2015-0009

Li Y, Choy K-W, Xie H-N, Chen M, He W-Y, Gong Y-F, Liu H-Y, Song Y-Q, Xian Y-X, Sun X-F, Chen X-J


This study was conducted to describe a prenatal case of congenital hydrocephalus and hemivertebrae with a 6q terminal deletion and to investigate the possible correlation between the genotype and phenotype of the proband. We performed an array-based comparative genomic hybridization (aCGH) analysis on a fetus diagnosed with congenital hydrocephalus and hemivertebrae. The deletion, spanning 10.06 Mb from 6q25.3 to 6qter, was detected in this fetus. The results of aCGH, karyotype and fluorescent in situ hybridization (FISH) analyses in the healthy parents were normal, which confirmed that the proband’s copy-number variant (CNV) was de novo. This deleted region encompassed 97 genes, including 28 OMIM genes. We discussed four genes (TBP, PSMB1, QKI and Pacrg) that may be responsible for hydrocephalus while the T gene may have a role in hemivertebra. We speculate that five genes in the 6q terminal deletion region were potentially associated with hemivertebrae and hydrocephalus in the proband.


Isolated 6q subtelomeric deletions are relatively rare, and few correlative studies have been reported. The most common clinical features include mental retardation, developmental delay, dysmorphic features, hypotonia, microcephaly, facial dysmorphism, seizures, cardiac defects and brain anomalies, such as abnormal corpus callosum and hydrocephalus. Patients with pure 6q terminal deletions usually present multiple anomalies and seldom present less than three malformations. Hydrocephalus associated with a chromosome 6q terminal deletion has been reported in several postnatal and prenatal cases. However, the relationship between the involved region and the genes associated with hydrocephalus is still not well understood. Studies on hemivertebra due to microdeletions of distal chromosomal regions of 6q are scarce. This malformation often emerges simultaneously with various anomalies of the nervous system, musculoskeletal system, genitourinary tract, cardiac system and gastrointestinal tract, but no report discussing the possible genetic etiology has been published. Here we report on a 24-week-old fetus with congenital hydrocephalus and hemivertebrae diagnosed by prenatal ultrasonography with the molecular genetic finding of a 6q terminal deletion. The case described here is rare in that the proband only exhibited two of the deformities that have previously been reported to be associated with terminal 6q deletions. We investigated the genotype-phenotype correlation and sought to identify the relevant region of
the 6q terminus and the associated genes that may be responsible for these clinical features.

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Key Words

Genotype | Hemivertebrae | Hydrocephalus | Phenotype | 6q Terminal deletion