A 6q14.1‐q15 microdeletion in a male patient with severe autistic disorder, lack of oral language, and dysmorphic features with concomitant presence of a maternally inherited Xp22.31 copy number gain

Quintela, Inés; Prieto, Montse Fernández; Gomez-Guerrero, Lorena; Resches, Mariela; Eirís-Puñal, Jesús; Barros, Francisco; Carracedo, Ángel

doi:10.1002/ccr3.255

Cited by 4 publications

(7 citation statements)

References 43 publications

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“…Of these, 20 individuals (13 males and 7 females) had a proximal 6q deletion and could be included in our parent cohort. We further compiled a cohort of 25 literature cases (12 males and 13 females) from 13 published papers [ 7 – 19 ]. The median age (years; months) of individuals in the parent cohort was 5; 5 (range 0; 1–24; 11), and in the literature cohort was 5; 0 (range 0; 2–22; 0).…”

Section: Resultsmentioning

confidence: 99%

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The phenotypic spectrum of proximal 6q deletions based on a large cohort derived from social media and literature reports

et al. 2018

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Proximal 6q (6q11-q15) deletions are extremely rare and little is known about their phenotypic consequences. Since parents and caregivers now use social media to seek information on rare disorders, the Chromosome 6 Project has successfully collaborated with a Facebook group to collect data on individuals worldwide. Here we describe a cohort of 20 newly identified individuals and 25 literature cases with a proximal 6q deletion. Microarray results and phenotype data were reported directly by parents via a multilingual online questionnaire. This led to phenotype descriptions for five subregions of proximal 6q deletions; comparing the subgroups revealed that 6q11q14.1 deletions presented less severe clinical characteristics than 6q14.2q15 deletions. Gastroesophageal reflux, tracheo/laryngo/bronchomalacia, congenital heart defects, cerebral defects, seizures, and vision and respiratory problems were predominant in those with 6q14.2q15 deletions. Problems related to connective tissue (hypermobility, hernias and foot deformities) were predominantly seen in deletions including the COL12A1 gene (6q13). Congenital heart defects could be linked to deletions of MAP3K7 (6q15) or TBX18 (6q14.3). We further discuss the role of ten genes known or assumed to be related to developmental delay and/or autism (BAI3, RIMS1, KCNQ5, HTR1B, PHIP, SYNCRIP, HTR1E, ZNF292, AKIRIN2 and EPHA7). The most influential gene on the neurodevelopmental phenotype seems to be SYNCRIP (6q14.3), while deletions that include more than two of these genes led to more severe developmental delay. We demonstrate that approaching individuals via social media and collecting data directly from parents is a successful strategy, resulting in better information to counsel families.

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Section: Resultsmentioning

confidence: 99%

“…Patient Id116 also has a partial duplication of 6q14.1 (indicated by a white bar). The literature cases were derived from 13 reports [ 7 – 19 ]. See supplementary Table S 1 for details …”

Section: Methodsmentioning

confidence: 99%

The phenotypic spectrum of proximal 6q deletions based on a large cohort derived from social media and literature reports

et al. 2018

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“…We performed a literature review of clinical findings of proximal 6q deletion cases overlapping with our case [McNeal et al, 1977;Young et al, 1985;Yamamoto et al, 1986;Lonardo et al, 1988;Slater et al, 1988;Turleau et al, 1988;Valtat et al, 1992;Gershoni-Baruch et al, 1996;Romie et al, 1996;Hopkin et al, 1997;Kumar et al, 1997;Myers and Challman, 2005;Lespinasse et al, 2009;Van Esch et al, 2010;Wentzel et al, 2010;Woo et al, 2010;Becker et al, 2012;Quintela et al, 2015;Duarte et al, 2016]. In the majority of the cases, developmental delay and craniofacial features were common and variable.…”

Section: Discussionmentioning

confidence: 59%

Proximal Deletion of 6q Overlapping with Toriello-Carey Facial Phenotype: Prenatal Findings, Clinical Course, Differential Diagnosis, and Review

Catena¹,

Aracena²,

Pizarro³

et al. 2017

Mol Syndromol

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Proximal deletion of 6q is a relatively rare chromosomal abnormality. Reported patients have deletions of different sizes but share partial overlap and present with similar clinical features, and some of them were described prior to the introduction of chromosome microarrays. We describe a male patient with prenatal sonographic findings of nuchal edema, intrauterine growth restriction, renal pelvis dilatation, and oligohydramnios. At birth, facial dysmorphism, retro/micrognathia, a short and wide neck as well as cardiovascular and renal anomalies were noted. His clinical evolution has been marked by failure to thrive, severe developmental delay, and cognitive impairment. The diagnosis of Toriello-Carey syndrome (TCS) was based on his “gestalt.” aCGH identified a de novo proximal deletion of 17 Mb in 6q (6q12q14.3). Deletion 6q13q14 seems to be responsible for the main facial features and should be considered within the differential diagnosis of TCS.

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“…Despite the severe effects of haploinsufficiency of genes located at Xp22.3, there is increasing evidence that duplications in this region may represent benign variants with no significant pathognomonic nature [12,16]. Indeed, duplications of the steroid sulfatase (STS) gene, located in PAR1, have been reported in both males and females but without clinical significance [25,26].…”

Section: Discussionmentioning

confidence: 99%

“…However, it is not yet clarified if they consist pathogenic or benign variants. For example, duplications at the sub-telomeric Xp have been considered as causative or risk factors for myoskeletal, neurocognitive, or behavioral phenotypes [12][13][14][15][16]. To explain these discrepancies, Liu et al (2011) proposed a genomic dosage model that implies the combination of two or more genetic alterations in an individual who presents a clinical phenotype, which is otherwise not as severe or not as penetrant [12].…”

Section: Introductionmentioning

confidence: 99%

Unbalanced X;9 translocation in an infertile male with de novo duplication Xp22.31p22.33

Roumelioti

Louizou²,

Karras

et al. 2019

J Assist Reprod Genet

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Purpose Male carriers of an X-autosome translocation are generally infertile, regardless of the position of the breakpoint on the X chromosome while the pathogenicity of Xp22.3 subtelomeric duplications is under debate. To shed light into this controversy, we present a rare case, of an azoospermic male with no other significant clinical findings, in whom classical cytogenetics revealed additional unbalanced chromosomal material, at the telomere of the long arm of one homolog of chromosome 9. Methods In peripheral blood specimens of the index case and his parents, we performed GBanding, Inverted-DAPI Banding, AgNOR staining, Telomere specific Fluorescence in Situ Hybridization (FISH), Molecular karyotyping by Multi-color FISH, whole genome SNP microarrays, sub-telomeric MLPA, and transcription analysis of the expression of KAL1 gene by RT-PCR. Results Multi-color FISH revealed an unbalanced translocation involving the short arm of chromosome X. SNP microarray analysis combined to classical cytogenetics and MLPA demonstrated a de novo 8.796 Mb duplication of Xp22.31-p22.33. Compared to three control specimens, the patient presented significantly elevated expression levels of KAL1 mRNA in peripheral blood, suggesting transcriptional functionality of the duplicated segment. Conclusions The duplicated segment contains the pseudo-autosomal region PAR1 and more than 30 genes including SHOX, ARSE, STS, KAL1, and FAM9A and is not listed as polymorphic. Our data advocate that duplications of the Xp22.3 region may not be associated with a clinical consequence.

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A 6q14.1‐q15 microdeletion in a male patient with severe autistic disorder, lack of oral language, and dysmorphic features with concomitant presence of a maternally inherited Xp22.31 copy number gain

Cited by 4 publications

References 43 publications

The phenotypic spectrum of proximal 6q deletions based on a large cohort derived from social media and literature reports

The phenotypic spectrum of proximal 6q deletions based on a large cohort derived from social media and literature reports

Proximal Deletion of 6q Overlapping with Toriello-Carey Facial Phenotype: Prenatal Findings, Clinical Course, Differential Diagnosis, and Review

Unbalanced X;9 translocation in an infertile male with de novo duplication Xp22.31p22.33

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