Duplication of 10q22.3–q23.3 encompassing BMPR1A and NGR3 associated with congenital heart disease, microcephaly, and mild intellectual disability

Abstract

Chromosome region 10q22.3-q23.3 contains several low copy repeats (LCRs) and is prone to recombination. Deletions with breakpoints within LCR3 and LCR4 have been described to be associated with intellectual disability and dysmorphic features, while the reciprocal duplications are rarely reported. We present an additional case with multiple congenital anomalies that include microcephaly, cardiac defect, and mild intellectual disability, in which a de novo interstitial 8.2-Mb duplication of 10q22.3-q23.3, including BMPR1A and NGR3, was identified by Illumina SNP array platform. Our study is consistent with the hypothesis that the BMPR1A is a plausible candidate gene for congenital heart disease (CHD) and should contribute to the diagnosis and treatment of these genomic diseases.

A sex-stratified genome-wide association study of tuberculosis using a multi-ethnic genotyping array

“…Among the top hits in the logistic regression analysis (Table 6) some could impact TB susceptibility as they are involved in immune functions. The most significant interaction was between rs2631914 (LINCO2153), which is upregulated in people with major depressive disorder (58) and rs8067702 (RTN4RL1), previously associated with congenital heart disease, microcephaly and mild intellectual disability (59). While this interaction is not very informative in the context of TB three other interactions were identified that could impact TB susceptibility ( Table 6).…”

Interstitial 10q21.1q23.31 Duplication due to Meiotic Recombination of a Paternal Balanced Complex Rearrangement: Cytogenetic and Molecular Characterization

“…Some potential causative genes have been identified in the critical region 10q23.1q23.31. In particular, overexpression of BMPR1A and PTEN has been considered to be implicated in congenital heart disease [Crackower et al, 2002;Gaussin et al, 2002], while NGR3 , which plays an important role in early mammary morphogenesis, could contribute to limb malformation and short stature [Tang et al, 2015].…”

“…Individuals harboring smaller interstitial duplications (10q22.3q23.3) are also known, presenting with microcephaly, cardiac defects, and developmental, speech, and motor delay [van Bon et al, 2011;Tang et al, 2015].…”

Two de novo Overlapping Interstitial Duplications at 10q22 Associated with Speech Impairments, Behaviour Problems, Genital Anomalies, Developmental Delay and Intellectual Disability

“…Recurrent deletions at 10q22.3q23.3 mediated by LCR3-4 are associated with intellectual disability, developmental delay, dysmorphic features, behavior problems and other neurodevelopmental disorders, whereas reciprocal duplications are contributed to distinctive facial features, cognitive impairments, congenital heart disease, and delays in language and motor development. Interstitial deletions or duplications at 10q22.3q23.3 are infrequently reported, and a distinct clinically recognizable syndrome has not emerged [2][3][4][5][6][7][8][9][10].…”

“…To date, only eight patients with de novo deletions at 10q22 have been reported, and the main clinical features include speech impairments, dysmorphic features, genital anomalies, intellectual disability and developmental delay [7,[11][12][13][14][15]. Dufke and Han each described a case with a de novo duplication at 10q22.2q22.3~23.1 and 10q22q24 detected by G-banding analysis respectively, whereas the two segments not only covered the 10q22 region but also LCR3-4 which was demonstrated to be clinically significant [8][9][10]16,17]. Here, we report two unrelated patients with de novo overlapping duplications at the 10q22 interval that are 6.4 Mb and 9.8 Mb in size separately, detected by high-resolution CMA.…”