Clinical and genomic characterization of siblings with a distal duplication of chromosome 9q (9q34.1‐qter)

Mizuno, Seiji; Fukushi, Daisuke; Kimura, Ryoji; Yamada, Kenichiro; Yamada, Yasukazu; Kumagai, Toshiyuki; Wakamatsu, Nobuaki

doi:10.1002/ajmg.a.34160

Cited by 6 publications

(7 citation statements)

References 5 publications

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“…A 9q34 duplication syndrome (9q34 DS) has been reported [10], involving both interstitial [11][12][13][14] and terminal [1,10,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] duplications, with different sizes. The associated manifestations include initial poor feeding and thriving, hypotonia, DD, mostly affecting speech and language, ID, craniofacial dysmorphisms and other musculoskeletal anomalies.…”

Section: Introductionmentioning

confidence: 99%

9q34.3 microduplications lead to neurodevelopmental disorders through EHMT1 overexpression

et al. 2019

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Both copy number losses and gains occur within subtelomeric 9q34 region without common breakpoints. The microdeletions cause Kleefstra syndrome (KS), whose responsible gene is EHMT1. A 9q34 duplication syndrome (9q34 DS) had been reported in literature, but it has never been characterized by a detailed molecular analysis of the gene content and endpoints. To the best of our knowledge, we report on the first patient carrying the smallest 9q34.3 duplication containing EHMT1 as the only relevant gene. We compared him to 21 reported patients described here as carrying 9q34.3 duplications encompassing the entire gene and extending within ~3 Mb. By surveying

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Section: Introductionmentioning

confidence: 99%

9q34.3 microduplications lead to neurodevelopmental disorders through EHMT1 overexpression

et al. 2019

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“…). cEDS phenotype has not been reported in three of five cases with a pure 9q34 duplication encompassing COL5A1 (Mizuno et al ; Gadancheva et al ; Natera‐de Benito et al ).…”

Section: Discussionmentioning

confidence: 99%

“…Multi-exon deletions and duplications in COL5A1 are expected to strongly contribute to the pathogenesis of cEDS. Only five cases with pure distal duplication of 9q34 have been reported (Mizuno et al 2011;Singh et al 2012;Gadancheva et al 2014;Natera-de Benito et al 2015) (Fig. 3).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a patient with classical Ehlers‐Danlos syndrome due to a 9q34 duplication affecting COL5A1

Kuroda

Ohashi

Naruto

et al. 2018

Congenital Anomalies

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Ehlers-Danlos syndrome classical type is a connective tissue disorder characterized by skin hyperextensibility, atrophic scarring, and joint hypermobility. The condition typically results from mutations in COL5A1 or COL5A2 leading to the functional haploinsufficiency. Here, we report of a 24-year-old male with mild intellectual disability, dysmorphic features, and a phenotype consistent with Ehlers-Danlos syndrome classical type. A copy number variant-calling algorithm from panel sequencing data identified the deletions exons 2-11 and duplications of exons 12-67 within COL5A1. Array comparative genomic hybridization confirmed a 94 kb deletion at 9q34.3 involving exons 2-11 of COL5A1, and a 3.4 Mb duplication at 9q34.3 involving exons 12-67 of COL5A1.

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“…Until now, there were almost 50 cases reported in DECIPHER (Database of Chromosomal Imbalance and Phenotype in Human using Ensembl Resources), which overlapped with the 9qter region we have found. A 3.0–3.4 Mb region (9q34.11-34.13) was proposed to be critical for the presentation of several phenotypes associated with 9q34 duplications [ 9 , 10 ]. The key features included characteristic facial appearance, long fingers and toes, slight psychomotor retardation, heart murmur et al…”

Section: Discussionmentioning

confidence: 99%

A de novo duplication of chromosome 9q34.13-qter in a fetus with Tetralogy of Fallot Syndrome

Liu

et al. 2016

Mol Cytogenet

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BackgroundPartial duplications of the distal 9q have been rarely reported in literatures. The key features included characteristic facial appearance, long fingers and toes, slight psychomotor retardation, heart murmur et al. But rare severe congenital heart defects (CHD) such as TOF were reported to be associated with 9qter duplications.Case presentationA 23-year-old woman was referred for genetic counseling and prenatal diagnosis at 253/7 weeks of gestation due to her male fetus, diagnosed as Tetralogy of Fallot Syndrome (TOF) by prenatal ultrasound. SNP (Single nucleotide polymorphism) array revealed that the male fetus had a de novo 5.47 Mb duplication at 9q34.13-qter. Meanwhile, non-invasive prenatal testing (NIPT) using low coverage whole genome massively parallel sequencing of circulating cell-free fetal DNA (cffDNA) showed consistent results. Multiplex ligation-dependent probe amplification (MLPA) also confirmed the duplication at 9qter.ConclusionIn this paper, we present an Asian fetus with TOF caused by a de novo 5.47 Mb duplication at 9q34.13-qter. Duplication of 9q34.13-qter should be considered as an etiological diagnosis in the case of TOF. Our prenatal diagnostic findings provide important information for genetic counseling on the male fetus and future pregnancies in this family. Chromosomal microarray analysis (CMA) remains the first-tier clinical diagnostic test for prenatal fetus with suspicious syndromes. We also highlight the high potential application of NIPT in the screening of sub-chromosomal rearrangement.

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Clinical and genomic characterization of siblings with a distal duplication of chromosome 9q (9q34.1‐qter)

Cited by 6 publications

References 5 publications

9q34.3 microduplications lead to neurodevelopmental disorders through EHMT1 overexpression

9q34.3 microduplications lead to neurodevelopmental disorders through EHMT1 overexpression

Evaluation of a patient with classical Ehlers‐Danlos syndrome due to a 9q34 duplication affecting COL5A1

A de novo duplication of chromosome 9q34.13-qter in a fetus with Tetralogy of Fallot Syndrome

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