Diagnostic Yield of Molecular Karyotyping of Idiopathic Intellectual Disability Patients Ended with One Causative Anomaly; Duplication 9q34 Syndrome

  • Büşranur Çavdarlı Ankara Numune Training and Research Hospital
  • Emriye Ferda Perçin
  • Meral Yirmibeş Karaoğuz
  • Mehmet Ali Ergün
Keywords: Intellectual disability, microarray analysis, chromosome 9q34 duplication, microduplication, FISH

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.

Author Biography

Büşranur Çavdarlı, Ankara Numune Training and Research Hospital
Medical Genetics

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.

Published
2019-06-21
Section
Original Research