A new chromosome 17q21.31 microdeletion syndrome associated with a common inversion polymorphism

Koolen, David A.; Vissers, Lisenka E.L.M.; Pfundt, Rolph; Leeuw, Nicole de; Knight, Samantha J. L.; Regan, Regina; Kooy, R. Frank; Reyniers, Edwin; Romano, Corrado; Fichera, Marco; Schinzel, Albert; Baumer, Alessandra; Anderlid, Britt Marie; Schoumans, Jacqueline; Knoers, Nine V A M; Kessel, Ad Geurts van; Sistermans, Erik A.; Veltman, Joris A.; Brunner, Han G.; Vries, Bert B.A. de

doi:10.1038/ng1853

Cited by 411 publications

(349 citation statements)

References 15 publications

Supporting

Mentioning

340

Contrasting

Unclassified

Order By: Relevance

“…The defects of genes coding for proteins responsible for microtubule function has previously been associated with neurodevelopmental disorders with dysmorphic features, 15 with MAPT representing one recent example. This gene is considered to be the candidate for the features of the recurrent 17q21 deletion syndrome, 16 which interestingly shows DD, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, as well as eye abnormalities among the recurrent features. It is therefore possible that WAC is one of the candidates for the DD, which is the only feature common in all seven patients.…”

Section: Molecular Results Of the Six Patients Are Summarised Inmentioning

confidence: 99%

Genomic and clinical characteristics of six patients with partially overlapping interstitial deletions at 10p12p11

et al. 2011

View full text Add to dashboard Cite

International audienceWith the clinical implementation of genomic microarrays, the detection of cryptic unbalanced rearrangements in patients with syndromic developmental delay has considerably improved. Here we report the molecular karyotyping and phenotypic description of six new unrelated patients with partially overlapping microdeletions at 10p12.31p11.21 ranging from 1.0 Mb to 10.6 Mb. The smallest region of overlap is 306 kb, which includes gene, known to be associated with microtubule function and to play a role in cell division. Another patient has previously been described with a 10 Mb deletion, partially overlapping with our six patients. All seven patients have developmental delay and a majority of the patients have abnormal behaviour and dysmorphic features including bulbous nasal tip, deep set eyes, synophrys/thick eyebrows, and full cheeks, while other features varied. All patients also displayed various visual impairments and 6 out of 7 patients had cardiac malformations. Together with the previously reported patient, our study suggests that the detected deletions may represent a new contiguous gene syndrome caused by dosage sensitive genes that predispose to developmental delay

show abstract

Section: Molecular Results Of the Six Patients Are Summarised Inmentioning

confidence: 99%

Genomic and clinical characteristics of six patients with partially overlapping interstitial deletions at 10p12p11

et al. 2011

View full text Add to dashboard Cite

show abstract

“…A search of the medical literature identified 23 articles describing the clinical features of 81 patients with KdVS. [1][2][3][4][5]13,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] …”

Section: Methodsmentioning

confidence: 99%

“…[1][2][3] The syndrome can be either caused by a microdeletion in chromosomal region 17q21. 31 or by a truncating variant in the KAT8 regulatory NSL complex unit 1 (KANSL1) gene (NG_032784.1).…”

Section: Introductionmentioning

confidence: 99%

The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

et al. 2015

Self Cite

View full text Add to dashboard Cite

The Koolen-de Vries syndrome (KdVS; OMIM #610443), also known as the 17q21.31 microdeletion syndrome, is a clinically heterogeneous disorder characterised by (neonatal) hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism. Expressive language development is particularly impaired compared with receptive language or motor skills. Other frequently reported features include social and friendly behaviour, epilepsy, musculoskeletal anomalies, congenital heart defects, urogenital malformations, and ectodermal anomalies. The syndrome is caused by a truncating variant in the KAT8 regulatory NSL complex unit 1 (KANSL1) gene or by a 17q21.31 microdeletion encompassing KANSL1. Herein we describe a novel cohort of 45 individuals with KdVS of whom 33 have a 17q21.31 microdeletion and 12 a single-nucleotide variant (SNV) in KANSL1 (19 males, 26 females; age range 7 months to 50 years). We provide guidance about the potential pitfalls in the laboratory testing and emphasise the challenges of KANSL1 variant calling and DNA copy number analysis in the complex 17q21.31 region. Moreover, we present detailed phenotypic information, including neuropsychological features, that contribute to the broad phenotypic spectrum of the syndrome. Comparison of the phenotype of both the microdeletion and SNV patients does not show differences of clinical importance, stressing that haploinsufficiency of KANSL1 is sufficient to cause the full KdVS phenotype.

show abstract

“…[1][2][3][4] The syndrome is caused by a recurrent 500-650 kb heterozygous deletion at chromosome 17q21.31, [5][6][7] which is thought to result from nonallelic homologous recombination (NAHR), 8 mediated by flanking low-copy repeats. The minimum critical region is 424 kb (41 046 729-41 470 954 Mb, hg18) in size 1 and encompasses four known genes, CRHR1, IMP5, MAPT, and STH, in addition to three putative genes, FLJ25168, BC018035, and LOC284058.…”

Section: Introductionmentioning

confidence: 99%

Two families with sibling recurrence of the 17q21.31 microdeletion syndrome due to low-grade mosaicism

et al. 2012

Self Cite

View full text Add to dashboard Cite

The 17q21.31 microdeletion syndrome is characterised by intellectual disability, epilepsy, distinctive facial dysmorphism, and congenital anomalies. To date, all individuals reported with this syndrome have been simplex patients, resulting from de novo deletions. Here, we report sibling recurrence of the 17q21.31 microdeletion syndrome in two independent families. In both families, the mother was confirmed to be the parent-of-origin for the 17q21.31 deletion. Fluorescence in situ hybridisation analyses in buccal mucosa cells, of the mother of family 1, identified monosomy 17q21.31 in 4/50 nuclei (8%). In mother of family 2, the deletion was identified in 2/60 (3%) metaphase and in 3/100 (3%) interphase nuclei in peripheral lymphocytes, and in 7/100 (7%) interphase nuclei in buccal cells. A common 17q21.31 inversion polymorphism predisposes to non-allelic homologous recombination and hereby to the 17q21.31 microdeletion syndrome. On the basis of the 17q21.31 inversion status of the parents, we calculated that the probability of the second deletion occurring by chance alone was 1/14 438 and 1/4812, respectively. If the inversion status of the parents of a child with the 17q21.31 microdeletion syndrome is unknown, the overall risk of a second child with the 17q21.31 microdeletion is 1/9461. We conclude that the presence of low-level maternal somatic-gonadal mosaicism is associated with the microdeletion recurrence in these families. This suggests that the recurrence risk for parents with a child with a 17q21.31 microdeletion for future pregnancies is higher than by chance alone and testing for mosaicism in the parents might be considered as a helpful tool in the genetic counselling.

show abstract

A new chromosome 17q21.31 microdeletion syndrome associated with a common inversion polymorphism

Cited by 411 publications

References 15 publications

Genomic and clinical characteristics of six patients with partially overlapping interstitial deletions at 10p12p11

Genomic and clinical characteristics of six patients with partially overlapping interstitial deletions at 10p12p11

The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant

Two families with sibling recurrence of the 17q21.31 microdeletion syndrome due to low-grade mosaicism

Contact Info

Product

Resources

About