Chromosome 15q11-q13 copy number gain detected by array-CGH in two cases with a maternal methylation pattern

Molecular Cytogenetics

Ene-Choo Tan⁴  Maggie SY Brett²  Zhi-hui Li⁵  Eileen CP Lim²  Min-Hwee Yong³  Ee-Shien Tan¹ 

[1] Genetics Service, KK Women’s & Children’s Hospital, 100 Bukit Timah Road 229899 Singapore, Singapore;KK Research Laboratory, KK Women’s & Children’s Hospital, 100 Bukit Timah Road 229899 Singapore, Singapore;Cytogenetics Laboratory, KK Women’s & Children’s Hospital, 100 Bukit Timah Road 229899 Singapore, Singapore;Office of Clinical Sciences, Duke-NUS Graduate Medical School, 8 College Road 169857 Singapore, Singapore;Genomax Technologies Pte Ltd, 51 Science Park Road, #04-15 117586 Singapore, Singapore

关键词: Marker chromosome;    Fluorescence in situ hybridization (FISH);    Developmental delay;    Autism;    Copy number gain;    Array comparative genomic hybridization (aCGH);    15q duplication syndrome;   

Others  :  1150111
DOI  :  10.1186/1755-8166-7-32

 received in 2014-02-27, accepted in 2014-04-11,  发布年份 2014

【 摘 要 】

Background

The 15q11-q13 region contains many low copy repeats and is well known for its genomic instability. Several syndromes are associated with genomic imbalance or copy-number-neutral uniparental disomy. We report on two patients: Patient 1 is a boy with developmental delay and autism; and Patient 2 is a girl with developmental delay, hypotonia and dysmorphism. We performed analyses to delineate their dosage in the 15q region, determine whether the patients’ dosage correlates with phenotypic severity, and whether genes in the amplified regions are significantly associated with identified functional networks.

Results

For the proximal region of 15q, molecular cytogenetic analysis with Agilent oligonucleotide array showed a copy number of 3 for Patient 1 and a copy number of 4 for Patient 2. Fluorescent in situ hybridization analysis of Patient 2 showed two different populations of cells with different marker chromosomes. Methylation analysis of the amplified region showed that the extra copies of small nuclear ribonucleoprotein polypeptide N gene were of maternal origin. Phenotypic severity did not correlate with the size and dosage of 15q, or whether the amplification is interstitial or in the form of a supernumerary marker. Pathway analysis showed that in Patient 2, the main functional networks that are affected by the genes from the duplicated/triplicated regions are developmental disorder, neurological disease and hereditary disease.

Conclusions

The 15q11-q13 gains that were found in both patients could explain their phenotypic presentations. This report expands the cohort of patients for which 15q11-q13 duplications are molecularly characterized.

【 授权许可】

   
2014 Tan et al.; licensee BioMed Central Ltd.

【 图 表 】

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