Genetic heterogeneity of patients with suspected Silver-Russell syndrome: genome-wide copy number analysis in 82 patients without imprinting defects

Autor: Kazuki Yamazawa, Tomoko Fuke, Zenro Kizaki, Yoshika Matsukura, Hisakazu Nakajima, Keiko Matsubara, Takanobu Inoue, Tsutomu Ogata, Akira Oka, Maki Fukami, Chie Harashima, Seiji Mizuno, Akie Nakamura, Masayo Kagami, Kumi Tsumura, Shinichiro Sano, Tatsuji Hasegawa
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
Pathogenic copy number variation
lcsh:QH426-470
DNA Copy Number Variations
Heart Diseases
Developmental Disabilities
Williams syndrome
Copy number analysis
Short Report
lcsh:Medicine
030105 genetics & heredity
Biology
Bioinformatics
4p microdeletion syndrome
Epigenesis
Genetic
Mosaic trisomy 18
03 medical and health sciences
Genetic Heterogeneity
Genomic Imprinting
Young Adult
parasitic diseases
Genetics
medicine
Humans
Copy-number variation
Global developmental delay
Child
Molecular Biology
Genetics (clinical)
Comparative Genomic Hybridization
Genetic heterogeneity
Silver–Russell syndrome
lcsh:R
Brachydactyly
Netchine-Harbison clinical scoring system
Infant
DNA Methylation
medicine.disease
lcsh:Genetics
Silver-Russell Syndrome
19q13.11 deletion syndrome
030104 developmental biology
Array comparative genomic hybridization
Child
Preschool
Female
Trisomy
Developmental Biology
Congenital disorder
Zdroj: Clinical Epigenetics
Clinical Epigenetics, Vol 9, Iss 1, Pp 1-10 (2017)
ISSN: 1868-7083
Popis: Background Silver-Russell syndrome (SRS) is a rare congenital disorder characterized by pre- and postnatal growth failure and dysmorphic features. Recently, pathogenic copy number variations (PCNVs) and imprinting defects other than hypomethylation of the H19-differentially methylated region (DMR) and maternal uniparental disomy chromosome 7 have been reported in patients with the SRS phenotype. This study aimed to clarify the frequency and clinical features of patients with SRS phenotype caused by PCNVs. Methods We performed array comparative genomic hybridization analysis using a catalog array for 54 patients satisfying the Netchine-Harbison clinical scoring system (NH-CSS) (SRS-compatible) and for 28 patients presenting with three NH-CSS items together with triangular face and/or fifth finger clinodactyly and/or brachydactyly (SRS-like) without abnormal methylation levels of 9 DMRs related to known imprinting disorders. We then investigated the clinical features of patients with PCNVs. Results Three of the 54 SRS-compatible patients (5.6%) and 2 of the 28 SRS-like patients (7.1%) had PCNVs. We detected 3.5 Mb deletion in 4p16.3, mosaic trisomy 18, and 3.77–4.00 Mb deletion in 19q13.11-12 in SRS-compatible patients, and 1.41–1.97 Mb deletion in 7q11.23 in both SRS-like patients. Congenital heart diseases (CHDs) were identified in two patients and moderate to severe global developmental delay was observed in four patients. Conclusions Of the patients in our study, 5.6% of SRS-compatible and 7.1% of SRS-like patients had PCNVs. All PCNVs have been previously reported for genetic causes of contiguous deletion syndromes or mosaic trisomy 18. Our study suggests patients with PCNVs, who have a phenotype resembling SRS, show a high tendency towards CHDs and/or apparent developmental delay.
Databáze: OpenAIRE
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