Copy number variations in three children with sudden infant death

• Published in: Clinical genetics 2009-07, Vol.76 (1), p.63-68
• Main Authors: Toruner, GA, Kurvathi, R, Sugalski, R, Shulman, L, Twersky, S, Pearson, PG, Tozzi, R, Schwalb, MN, Wallerstein, R
• Format: Article
• Language: English
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; array-based comparative genomic hybridization; Biological and medical sciences; Child; Child, Preschool; Comparative Genomic Hybridization; copy number variation; Databases, Genetic; Deoxyribonucleic acid; DNA; Emergency and intensive care: neonates and children. Prematurity. Sudden death; Fatal Outcome; Fundamental and applied biological sciences. Psychology; Gene Dosage; General aspects. Genetic counseling; Genetics of eukaryotes. Biological and molecular evolution; Genome, Human - genetics; Genomics; Humans; Infant; Infant, Newborn; Intensive care medicine; Medical genetics; Medical sciences; Molecular and cellular biology; Risk factors; SIDS; Software; Sudden Infant Death - genetics; Sudden infant death syndrome; unclassified sudden infant death
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2009.01161.x

Sudden death of an infant is a devastating event that needs an explanation. When an explanation cannot be found, the case is labeled as sudden infant death syndrome or unclassified sudden infant death. The influence of genetic factors has been recognized for sudden infant death, but copy number variations (CNVs) as potential risk factors have not been evaluated yet. Twenty‐seven families were enrolled in this study. The tissue specimens from deceased children were obtained and array‐based comparative genomic hybridization (array‐CGH) experiments were performed on the genomic DNA isolated from these specimens using Agilent Technologies Custom 4 × 44K arrays. Quantitative polymerase chain reaction experiments were performed to confirm the overlapping duplication and deletion region in two different cases. A de novo CNV is detected in 3 of 27 cases (11%). In case 1, an ∼3‐Mb (chr 8: 143,211,215‐qter) duplication on 8q24.3‐qter and a 4.4‐Mb deletion on the 22q13.3‐qter (chr 22: 45,047,068‐qter) were detected. Subtelomeric chromosome analysis of the father and the surviving sibling of case 1 showed a balanced reciprocal translocation, 46,XY,t(8;22)(q24.3;q13.3). A 240‐kb (chr 6: 26,139,810‐26,380,787) duplication and a 1.9‐Mb deletion (chr 6: 26,085,971‐27,966,150) at chromosome 6p22 were found in cases 2 and 3, respectively. Array‐CGH and conventional cytogenetic studies did not reveal the observed CNVs in the parents and the siblings of cases 2 and 3. The detected CNVs in cases 2 and 3 encompassed several genes including the major histone cluster genes. Array‐CGH analysis may be beneficial during the investigations after sudden infant death.