Molecular characterization of a novel ring 6 chromosome using next generation sequencing.
BACKGROUND
Karyotyping is the gold standard cytogenetic method for detection of ring chromosomes. In this study we report the molecular characterization of a novel ring 6 (r6) chromosome in a six-year-old girl with severe mental retardation, congenital heart disease and craniofacial abnormalities.


METHODS
Cytogenetic analysis was performed by conventional karyotyping. Molecular genetic analyses were performed using high-resolution chromosome microarray analysis (CMA) and next generation sequencing (NGS). OMIM, UCSC and PubMed were used as reference databases to determine potential genotype to phenotype associations.


RESULTS
Peripheral blood and skin fibroblast karyotyping revealed the presence of a dominant cell line, 46,XX,(r6)(p25.3;q27) and a minor cell line 45,XX,-6. Molecular karyotyping using NGS identified 6p25.3 and 6q27 subtelomeric deletions of 1.78 Mb and a 0.56 Mb, respectively. Based on the known genes located within the r6 deletion interval 6q25.3-pter, genotype to phenotype association studies found compelling evidence to suggest that hemizygous expression of disease genes FOXC1, FOXF2, IRF4 and GMDS was the main underlying cause of the patient's phenotype. We further speculate that the severity of the patient's symptoms may have been exacerbated by low-level instability of the r6 chromosome.


CONCLUSIONS
This is the first report of a novel r6 chromosome characterized at the molecular level using NGS.
Center for Obstetrics and Prenatal Diagnosis, The Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, China.
Rui
R
Zhang
Center for Obstetrics and Prenatal Diagnosis, The Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, China.
Xuan
X
Chen
Department of Obstetrics and Gynaecology, The Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, China.
Peiling
P
Li
Center for Obstetrics and Prenatal Diagnosis, The Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, China.
Xiumin
X
Lu
Center for Obstetrics and Prenatal Diagnosis, The Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, China.
Yu
Y
Liu
Center for Obstetrics and Prenatal Diagnosis, The Second Affiliated Hospital of Harbin Medical University, 150000 Harbin, China.
Yan
Y
Li
Translational Medicine Center, Guangdong Women and Children's Hospital, Guangzhou, 511400 China.
Liang
L
Zhang
Berry Genomics Corporation, Building 9, No 6 Court Jingshun East Road, Chaoyang District, Beijing, 100015 China.
Mengnan
M
Xu
Berry Genomics Corporation, Building 9, No 6 Court Jingshun East Road, Chaoyang District, Beijing, 100015 China.
David S
DS
Cram
Chromosome microarray analysis; Copy number variation; Karyotyping; Next generation sequencing; Ring chromosome