Clinical and molecular characterization of 17q21.31 microdeletion syndrome in 14 French patients with mental retardation

Dubourg, Christèle; Sanlaville, Damien; Doco‐Fenzy, Martine; Caignec, Cédric Le; Missirian, Chantal; Jaillard, Sylvie; Schluth-Bolard, Caroline; Landais, Emilie; Boute, Odile; Philip, Nicole; Toutain, Annick; David, Albert; Edery, Patrick; Moncla, Anne; Martin‐Coignard, Dominique; Vincent‐Delorme, Catherine; Mortemousque, Isabelle; Duban‐Bedu, Bénédicte; Drunat, Séverine; Béri, Mylène; Mosser, Jean; Odent, Sylvie; David, Véronique; Andrieux, Joris

doi:10.1016/j.ejmg.2010.11.003

Cited by 49 publications

(67 citation statements)

References 32 publications

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“…This is similar to numbers in the medical literature (18-29%). 13,18,22 Postnatal growth retardation is present in 35%, which is also similar to the other larger cohorts of patients (18-36%). 13,22 Short stature, if present, was proportionate.…”

Section: Growth Parameterssupporting

confidence: 84%

“…13,18,20,22,30 In our cohort, we observed behavioural problems in 57% of cases. These problems included autism/autistic traits, ADHD/attention deficit/ hyperactivity, shyness, anxiety/phobias, impulsive and stereotypic behaviour, psychosis, and depression.…”

Section: Neuropsychological Disorderssupporting

confidence: 49%

“…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%

“…This has also been described by Tan el al. 22 Notably, Dubourg et al 18 and Wright et al 26 described patients with sensorineural hearing loss.…”

Section: Visual and Hearing Impairmentsmentioning

confidence: 99%

“…Persistent ductus arteriosus has been reported previously 13 as well as pulmonary stenosis, intracardiac non-obstructive lesions, bicuspid aortic valve, and a dilated aortic root. 18,22,26 Renal and urogenital anomalies Renal and urogenital anomalies were present in 45%. Cryptorchidism was present in 53% of the male patients.…”

Section: Cardiovascular Defectsmentioning

confidence: 99%

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

et al. 2015

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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.

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Section: Growth Parameterssupporting

confidence: 84%

Section: Neuropsychological Disorderssupporting

confidence: 49%

Section: Methodsmentioning

confidence: 99%

“…This has also been described by Tan el al. 22 Notably, Dubourg et al 18 and Wright et al 26 described patients with sensorineural hearing loss.…”

Section: Visual and Hearing Impairmentsmentioning

confidence: 99%

Section: Cardiovascular Defectsmentioning

confidence: 99%

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

et al. 2015

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De novo triplication of the MAPT gene from the recurrent 17q21.31 microdeletion region in a patient with moderate intellectual disability and various minor anomalies

Gregor

Krumbiegel

Kraus

et al. 2012

American J of Med Genetics Pt A

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We report on a 16-year-old male patient with moderate intellectual disability, behavioral problems, and further anomalies such as facial dysmorphism, heart defect, and urogenital anomalies. By molecular karyotyping we identified the first de novo copy number gain to four copies on chromosome 17q21.31 including the MAPT gene but not the entire recurrent microdeletion/microduplication region. Recurrent microdeletions of this region including the MAPT and the CHRH1 genes have been shown to be a relatively frequent cause of intellectual disability, while only a few reciprocal duplications in patients with variable cognitive disorders have been published so far. A common inversion polymorphism in this region has been linked to a distinct H2 haplotype and seems to be associated with an increased risk for microdeletions and -duplications. Our patient and his father were both heterozygous for the H1/H2 haplotype, whereas the mother was homozygous for the H2 haplotype. In our patient the dosage gain apparently occurred on the paternal H1 allele and did not involve the H2 allele as in the previously published cases. This patient further delineates the genotypic and phenotypic variability associated with copy number variants from the 17q21.31 microdeletion region.

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If not Angelman, what is it? a review of Angelman‐like syndromes

Tan

Bird

Thibert

et al. 2014

American J of Med Genetics Pt A

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Angelman syndrome (AS) is caused by a lack of expression of the maternally inherited UBE3A gene in the brain. However, about 10% of individuals with a clinical diagnosis of AS do not have an identifiable molecular defect. It is likely that most of those individuals have an AS-like syndrome that is clinically and molecularly distinct from AS. These AS-like syndromes can be broadly classified into chromosomal microdeletion and microduplication syndromes, and single-gene disorders. The microdeletion/microduplication syndromes are now easily identified by chromosomal microarray analysis and include Phelan–McDermid syndrome (chromosome 22q13.3 deletion), MBD5 haploinsufficiency syndrome (chromosome 2q23.1 deletion), and KANSL1 haploinsufficiency syndrome (chromosome 17q21.31 deletion). The single-gene disorders include Pitt–Hopkins syndrome (TCF4), Christianson syndrome (SLC9A6), Mowat–Wilson syndrome (ZEB2), Kleefstra syndrome (EHMT1), and Rett (MECP2) syndrome. They also include disorders due to mutations in HERC2, adenylosuccinase lyase (ADSL), CDKL5, FOXG1, MECP2 (duplications), MEF2C, and ATRX. Although many of these single-gene disorders can be caused by chromosomal microdeletions resulting in haploinsufficiency of the critical gene, the individual disorders are often caused by intragenic mutations that cannot be detected by chromosomal microarray analysis. We provide an overview of the clinical features of these syndromes, comparing and contrasting them with AS, in the hope that it will help guide clinicians in the diagnostic work-up of individuals with AS-like syndromes.

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Clinical and molecular characterization of 17q21.31 microdeletion syndrome in 14 French patients with mental retardation

Cited by 49 publications

References 32 publications

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

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

De novo triplication of the MAPT gene from the recurrent 17q21.31 microdeletion region in a patient with moderate intellectual disability and various minor anomalies

If not Angelman, what is it? a review of Angelman‐like syndromes

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