Homozygous 16p13.11 duplication associated with mild intellectual disability and urinary tract malformations in two siblings born from consanguineous parents

Houcinat, Nada; Llanas, Brigitte; Moutton, Sébastien; Toutain, Jérôme; Cailley, Dorothée; Arveiler, Benoı̂t; Combe, C.; Lacombe, Didier; Rooryck, Caroline

doi:10.1002/ajmg.a.37212

Cited by 14 publications

(9 citation statements)

References 26 publications

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“…Although this variant does not explain the left renal dysplasia, it could be a risk factor for neurodevelopmental disorders and colorectal tumorigenesis [25,26]. However, there are rare reports of 16p13.11 duplication casing a renal defect [27,28]. Whether or not 16p13.11 duplication is associated with renal development still needs to be further verified with larger samples.…”

Section: Discussionmentioning

confidence: 99%

Copy number variations associated with fetal congenital kidney malformations

Cai

Lin

et al. 2020

Mol Cytogenet

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Background: Congenital anomalies of the kidney and urinary tract (CAKUT) constitute 20-30% of all congenital malformations. Within the CAKUT phenotypic spectrum, renal hypodysplasia (RHD) is particularly severe. This study aimed to evaluate the applicability of single-nucleotide polymorphism (SNP) array test in prenatal diagnosis of RHD for improving prenatal genetic counseling and to search for evidence of a possible causative role of copy-number variations (CNVs) in RHD. Results: We performed a systematic survey of CNV burden in 120 fetuses with RHD: 103 cases were isolated RHD and 17 were non-isolated RHD. Single-nucleotide polymorphism (SNP) array test was performed using the Affymetrix CytoScan HD platform. All annotated CNVs were validated by fluorescence in situ hybridization. We identified abnormal CNVs in 15 (12.5%) cases of RHD; of these CNVs, 11 were pathogenic and 4 were variants of uncertain significance. The detection rate of abnormal CNVs in non-isolated RHD was higher (29.4%, 5/17) than that in isolated RHD (9.7%, 10/103) (P = 0.060). Parents are more inclined to terminate the pregnancy if the fetuses have pathogenic results of the SNP-array test. Conclusions: The variable phenotypes that abnormal CNVs may cause indicate the genetic counseling is needed for RHD cases.

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Section: Discussionmentioning

confidence: 99%

Copy number variations associated with fetal congenital kidney malformations

Cai

Lin

et al. 2020

Mol Cytogenet

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“…Other identified studies included a case report of PUV with chronic renal disease in a child with mild intellectual disability carrying a homozygous 16p13.11 duplication [Houcinat et al, 2015], which we did not replicate in this study. As several of the CNV regions that we identified have been previously associated with renal anomalies, despite the different embryonic origins for the kidney and the urethra, we also examined studies with reported CNVs in anomalies of the kidney and urinary tract.…”

Section: Discussionmentioning

confidence: 86%

Rare copy number variants implicated in posterior urethral valves

Boghossian

Sicko

Kay

et al. 2015

American J of Med Genetics Pt A

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The cause of posterior urethral valves (PUV) is unknown, but genetic factors are suspected given their familial occurrence. We examined cases of isolated PUV to identify novel copy number variants (CNVs). We identified 56 cases of isolated PUV from all live-births in New York State (1998–2005). Samples were genotyped using Illumina HumanOmni2.5 microarrays. Autosomal and sex-linked CNVs were identified using PennCNV and cnvPartition software. CNVs were prioritized for follow-up if they were absent from in-house controls, contained ≥10 consecutive probes, were ≥20 Kb in size, had ≤20% overlap with variants detected in other birth defect phenotypes screened in our lab, and were rare in population reference controls. We identified 47 rare candidate PUV-associated CNVs in 32 cases; one case had a 3.9 Mb deletion encompassing BMP7. Mutationsin BMP7 have been associated with severe anomalies in the mouse urethra. Other interesting CNVs, each detected in a single PUV case included: a deletion of PIK3R3 and TSPAN1, duplication/triplication in FGF12, duplication of FAT1—a gene essential for normal growth and development, a large deletion (>2 Mb) on chromosome 17q that involves TBX2 and TBX4, and large duplications (>1 Mb) on chromosomes 3q and 6q. Our finding of previously unreported novel CNVs in PUV suggests that genetic factors may play a larger role than previously understood. Our data show a potential role of CNVs in up to 57% of cases examined. Investigation of genes in these CNVs may provide further insights into genetic variants that contribute to PUV.

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“…Urinary tract malformations have also been reported in siblings born to consanguineous parents, with a duplication at 16p13.11 [5]. In a case reported by Houcinat, et al [5], two male children were born to a father with a known history of unilateral renal agenesis. Both children were found to have urinary malformations and a duplication at 16p13.11.…”

Section: Discussionmentioning

confidence: 96%