Diagnostic Yield of Molecular Karyotyping of Idiopathic Intellectual Disability Patients Ended with One Causative Anomaly; Duplication 9q34 Syndrome
Abstract
Objective: Clinical application of sequence comparative genomic hybridization has greatly contributed to the diagnosis of patients with multiple congenital anomalies, syndromic or non-syndromic intellectual disability. The idiopathic intellectual disability patients with normal karyotype and/or normal subtelomeric rearrangement analysis via Fluorescence in situ Hybridization (FISH), using genome-wide microarray platforms have detected chromosome abnormalities in up to 12% of cases. In this study, we aimed that evaluate the etiology of 9 patients with idiopathic intellectual disability and congenital malformations or dysmorphic features. Methods: We performed genom wide SNP 2.7 array, in the evaluation of 9 patients with idiopathic intellectual disability and congenital malformations or dysmorphic features as well as normal karyotype and normal subtelomeric rearrangement analysis by the usage of FISH technique. Results: As a causative anomaly, a 2.6 Mb microduplication on 9q34.2-q34.3 was observed only in one patient who has idiopathic mental retardation and multiple skeletal anomalies. Conclusion: Microarray technology is a highly diagnostic method that is recommended for individuals with intellectual disability and multiple congenital anomalies. Microarray analysis revealed a causal anomaly in one of nine patients (11%) consistent with the literature.References
Shaffer LG. American College of Medical Genetics guideline on the cytogenetic evaluation of the individual with developmental delay or mental retardation. Genet Med 2005; 7(9): 650-4.
Ravnan JB, Tepperberg JH, Papenhausen P, Lamb AN. Hedrick J, Eash D et al. Subtelomere FISH analysis of 11 688 cases: an evaluation of the frequency and pattern of subtelomere rearrangements in individuals with developmental disabilities. J Med Genet 2006; 43(6), 478-89.
Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010; 86:749–64.
Gijsbers ACJ, Schoumans J, Ruivenkamp CAL. Interpretation of Array Comparative Genome Hybridization Data: A Major Challenge. Cytogenet Genome Res 2011; 135: 222–7.
Vissers LE, Vries BB, Veltman JA, Genomic microarrays in mental retardation: from CNV to gene, from research to diagnosis. J Med Genet 2010; 47(5): 289-97.
Sagoo GS, Butterworth AS, Sanderson S, Shaw-Smith C, Higgins JP, Burton H. Array CGH in patients with learning disability (mental retardation) and congenital anomalies: updated systematic review and meta-analysis of 19 studies and 13,926 subjects. Genet Med 2009; 11: 139-46.
Lybaek H, Meza-Zepeda LA, Kresse SH, Høysaeter T, Steen VM, Houge G. Array-CGH finemapping of minor and cryptic HR-CGH detected genomic imbalances in 80 out of 590 patients with abnormal development. Eur J Hum Genet 2008; 16: 1318-28. https://www.nature.com/articles/ejhg200878
Shin S, Yu N, Choi J R, Jeong S, Lee KA. Routine chromosomal microarray analysis is necessary in Korean patients with unexplained developmental delay/mental retardation/autism spectrum disorder. Ann Lab Med 2015; 35(5): 510-8.
Allerdice PW, Eales B, Onyett H, Sprague W, Henderson K, Lefeuvre PA, Pal G. Duplication 9q34 syndrome. Am J Hum Genet 1983; 35 (5): 1005-19.
Youngs EL, McCord T, Hellings JA, Spinner NB, Schneider A, Butler MG. An 18-year follow-up report on an infant with a duplication of 9q34. Am J Med Genet A 2010; 152A (1): 230-3.
Mizuno S, Fukushi D, Kimura R, Yamada K, Yamada Y, Kumagai T, Wakamatsu N. Clinical and genomic characterization of siblings with a distal duplication of chromosome 9q (9q34.1-qter). Am J Med Genet A 2011; 155A (9): 2274-80.
Shalinder S, Ashton F, Marquis-Nicholson R, Love JM, Lan CC, Aftimos S et al. A novel 2.3 Mb microduplication of 9q34. 3 inserted into 19q13. 4 in a patient with learning disabilities. Case Reports in Pediatrics 2012.
Gijsbers AC, Bijlsma EK, Weiss MM, Bakker E, Breuning MH, Hoffer MJ, Ruivenkamp CA. A 400kb duplication, 2.4Mb triplication and 130kb duplication of 9q34.3 in a patient with severe mental retardation. Eur J Med Genet 2008; 51(5): 479-87.
Romain DR, Goldsmith J, Columbano-Green LM, Chapman CJ, Smythe RH, Parfitt RG. Partial monosomy 12p13.1-13.3. J Med Genet 1987; 24: 434–6.
Yokoyama M, Nishi Y, Yoshii J, Okubo K, Matsubara K. Identification and cloning of neuroblastoma-specific and nerve tissue-specific genes through compiled expression profiles. DNA Res 1996; 3: 311-20.
Yang L, Zhao J, Lu W, Li Y, Du X, Ning T et al. KIAA0649, a 1A6/DRIM-interacting protein with the oncogenic potential. Biochem Biophys Res Commun 2005; 334: 884-90.
