A rare de novo interstitial duplication of 15q15.3q21.2 in a boy with severe short stature, hypogonadism, global developmental delay and intellectual disability

Yuan, Haiming; Meng, Zhe; Zhang, Lina; Luo, Xiangyang; Liu, Liping; Chen, Mengfan; Li, Xinwei; Zhao, Weiwei; Liang, Liyang

doi:10.1186/s13039-016-0214-3

Cited by 6 publications

(9 citation statements)

References 26 publications

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“…As well as the BCL11A variant, individual 6 also carries a 15q15.3q21.1 duplication, and a contribution of this duplication to the phenotype, specifically to delayed skeletal maturation and short stature, cannot be excluded. 55 HbF was significantly elevated in all affected individuals in whom it was assessed, including all those with missense mutations in BCL11A (Figure 1D, Table 1). Notably, individual 1, carrying a missense mutation, had HbF levels similar to those seen for individual 5, carrying a frameshift mutation.…”

Section: Identification Of Mutations In Bcl11a In Individuals With Idmentioning

confidence: 98%

BCL11A Haploinsufficiency Causes an Intellectual Disability Syndrome and Dysregulates Transcription

Dias

Estruch

Graham

et al. 2016

The American Journal of Human Genetics

142

174

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Intellectual disability (ID) is a common condition with considerable genetic heterogeneity. Next-generation sequencing of large cohorts has identified an increasing number of genes implicated in ID, but their roles in neurodevelopment remain largely unexplored. Here we report an ID syndrome caused by de novo heterozygous missense, nonsense, and frameshift mutations in BCL11A, encoding a transcription factor that is a putative member of the BAF swi/snf chromatin-remodeling complex. Using a comprehensive integrated approach to ID disease modeling, involving human cellular analyses coupled to mouse behavioral, neuroanatomical, and molecular phenotyping, we provide multiple lines of functional evidence for phenotypic effects. The etiological missense variants cluster in the amino-terminal region of human BCL11A, and we demonstrate that they all disrupt its localization, dimerization, and transcriptional regulatory activity, consistent with a loss of function. We show that Bcl11a haploinsufficiency in mice causes impaired cognition, abnormal social behavior, and microcephaly in accordance with the human phenotype. Furthermore, we identify shared aberrant transcriptional profiles in the cortex and hippocampus of these mouse models. Thus, our work implicates BCL11A haploinsufficiency in neurodevelopmental disorders and defines additional targets regulated by this gene, with broad relevance for our understanding of ID and related syndromes.

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Section: Identification Of Mutations In Bcl11a In Individuals With Idmentioning

confidence: 98%

BCL11A Haploinsufficiency Causes an Intellectual Disability Syndrome and Dysregulates Transcription

Dias

Estruch

Graham

et al. 2016

The American Journal of Human Genetics

142

174

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“…A CNV is defined as gain or loss of a DNA segment ≥50 pb broadly scattered through a given genome 15 – 17 . On the other hand, some authors only apply the definition of CNV to DNA segments ≥1 kb 18 .…”

Section: Introductionmentioning

confidence: 99%

Small de novo CNVs as biomarkers of parental exposure to low doses of ionizing radiation of caesium-137

Costa

Pinto

Gonçalves

et al. 2018

Sci Rep

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The radiological accident in Goiania in 1987 caused a trail of human contamination, animal, plant and environmental by a radionuclide. Exposure to ionizing radiation results in different types of DNA lesions. The mutagenic effects of ionizing radiation on the germline are special concern because they can endures for several generations, leading to an increase in the rate of mutations in children of irradiated parents. Thus, to evaluate the biological mechanisms of ionizing radiation in somatic and germline cells, with consequent determination of the rate mutations, is extremely important for the estimation of genetic risks. Recently it was established that Chromosomal Microarray Analysis is an important tool for detecting wide spectra of gains or losses in the human genome. Here we present the results of the effect of accidental exposure to low doses of ionizing radiation on the formation of CNVs in the progeny of a human population accidentally exposed to Caesium-137 during the radiological accident in Goiânia, Brazil.

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“…Elçioglu et al [1997] described a patient with hypogonadism, dysmorphic facial features, hypotonia, developmental delay, Marfan-like features and intellectual disability, who carried a de novo interstitial inverted duplication involving bands 15q13.3q21.3. Recently, Yuan et al [2016] described an interstitial duplication of 15q15.3q21.1 in a 14-year-old boy with severe short stature, delayed bone age, hypogonadism, global developmental delay, and intellectual disability. A micropenis, small testes and low testosterone were detected in this patient.…”

Section: Discussionmentioning

confidence: 99%

“…A micropenis, small testes and low testosterone were detected in this patient. Yuan et al [2016] speculated that duplication of the EID1 gene may be responsible for the hypogonadism phenotype. EID1 is known to be coexpressed with the steroidogenic factor-1 (SF-1), which plays a critical role in the adrenal and reproductive development and function.…”

Section: Discussionmentioning

confidence: 99%

Williams Syndrome and 15q Duplication: Coincidence versus Association

2016

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Williams syndrome is a multisystem disorder caused by contiguous gene deletion in 7q11.23, commonly associated with distinctive facial features, supravalvular aortic stenosis, short stature, idiopathic hypercalcemia, developmental delay, joint laxity, and a friendly personality. The clinical features of 15q11q13 duplication syndrome include autism, mental retardation, ataxia, seizures, developmental delay, and behavioral problems. We report a rare case of a girl with genetically confirmed Williams syndrome and coexisting 15q duplication syndrome. The patient underwent treatment for central precocious puberty and later presented with primary amenorrhea. The karyotype revealed 47,XX,+mar. FISH analysis for the marker chromosome showed partial trisomy/tetrasomy for proximal chromosome 15q (15p13q13). FISH using an ELN-specific probe demonstrated a deletion in the Williams syndrome critical region in 7q11.23. To our knowledge, a coexistence of Williams syndrome and 15q duplication syndrome has not been reported in the literature. Our patient had early pubertal development, which has been described in some patients with Williams syndrome. However, years later after discontinuing gonadotropin-releasing hormone analogue treatment, she developed primary amenorrhea.

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A rare de novo interstitial duplication of 15q15.3q21.2 in a boy with severe short stature, hypogonadism, global developmental delay and intellectual disability

Cited by 6 publications

References 26 publications

BCL11A Haploinsufficiency Causes an Intellectual Disability Syndrome and Dysregulates Transcription

BCL11A Haploinsufficiency Causes an Intellectual Disability Syndrome and Dysregulates Transcription

Small de novo CNVs as biomarkers of parental exposure to low doses of ionizing radiation of caesium-137

Williams Syndrome and 15q Duplication: Coincidence versus Association

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