A Novel (Paternally Inherited) Duplication 13q31.3q32.3 in a 12-Year-Old Patient with Facial Dysmorphism and Developmental Delay

Atack, Edward; Fairtlough, H; Smith, Kath; Balasubramanian, Meena

doi:10.1159/000358538

Cited by 5 publications

(2 citation statements)

References 21 publications

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“…ArrayCGH (aCGH) was performed on genomic DNA extracted from peripheral blood lymphocytes. DNA was applied to an 8 × 60 K printed BlueGnome ISCA v2 oligo array and analysed as previously described [Atack et al, ]. Results obtained were confirmed through Fluorescence in situ hybridization (FISH) (Patients 1 and 2) and G‐band chromosome analysis (Patient 3).…”

Section: Methodsmentioning

confidence: 99%

Copy number variants in association with type 1 collagenopathy: Atypical osteogenesis imperfecta

Balasubramanian

Cartwright

Smith

et al. 2015

American J of Med Genetics Pt A

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We report a sibling-pair and a 4-year old child from two families with an atypical presentation in Osteogenesis imperfecta (OI). In the sib-pair, the older sibling initially came to medical attention due to a fracture history (Patient 1) and she was shown to have a COL1A2 mutation. In addition, she also had developmental delay, facial dysmorphism, and a history of frequent infections which led to a search for an alternate diagnosis. ArrayCGH revealed a 4.3 Mb duplication on chromosome 19q13.42q13.43, which was confirmed by FISH analysis. On further familial analysis, the younger sibling who had no previous fracture history was also found to have the COL1A2 mutation and tested positive for the 19q13.42q13.43 duplication (Patient 2). The 19q13 duplication appears to be the cause of intellectual disability in these siblings but given that this is a chromosomal duplication, it is still possible that there is an as yet unidentified cause that may account for the combined phenotype in this family. Patient 3 was a 4-year old child presenting with a femoral fracture, blue sclerae, developmental delay, and joint hypermobility. Genetic analyses confirmed a COL1A2 mutation but also revealed an 8.8 Mb deletion of 11q24.2q25, confirmed by G-band chromosome analysis. We discuss the differing phenotypes in patients presenting with atypical OI and stress the need to consider ancillary investigations in individuals presenting with heterogeneous phenotypic symptoms, not entirely attributable to OI.

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Section: Methodsmentioning

confidence: 99%

Copy number variants in association with type 1 collagenopathy: Atypical osteogenesis imperfecta

Balasubramanian

Cartwright

Smith

et al. 2015

American J of Med Genetics Pt A

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“…Thus, it is not unexpected that perturbation of the WNT/PCP pathway affects the specification of APS derivatives, namely, the AME and node (29). In addition, while the links between mutations in PCP signaling and neural tube defects are well established (6,(30)(31)(32), their involvement in HPE remains uncharted. NOTCH signaling, on the other hand, has been implicated in HPE only recently (33).…”

Section: Prdm15 Regulates the Transcription Of Notch And Wnt/pcp To O...mentioning

confidence: 99%

PRDM15 loss of function links NOTCH and WNT/PCP signaling to patterning defects in holoprosencephaly

et al. 2020

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Holoprosencephaly (HPE) is a congenital forebrain defect often associated with embryonic lethality and lifelong disabilities. Currently, therapeutic and diagnostic options are limited by lack of knowledge of potential disease-causing mutations. We have identified a new mutation in the PRDM15 gene (C844Y) associated with a syndromic form of HPE in multiple families. We demonstrate that C844Y is a loss-of-function mutation impairing PRDM15 transcriptional activity. Genetic deletion of murine Prdm15 causes anterior/posterior (A/P) patterning defects and recapitulates the brain malformations observed in patients. Mechanistically, PRDM15 regulates the transcription of key effectors of the NOTCH and WNT/PCP pathways to preserve early midline structures in the developing embryo. Analysis of a large cohort of patients with HPE revealed potentially damaging mutations in several regulators of both pathways. Our findings uncover an unexpected link between NOTCH and WNT/PCP signaling and A/P patterning and set the stage for the identification of new HPE candidate genes.

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Eye Abnormalities in Patients With Chromosomal Disorders

Powell¹,

Pandya²,

Saif³

et al. 2019

Ophthalmic Genetic Diseases

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A Novel (Paternally Inherited) Duplication 13q31.3q32.3 in a 12-Year-Old Patient with Facial Dysmorphism and Developmental Delay

Cited by 5 publications

References 21 publications

Copy number variants in association with type 1 collagenopathy: Atypical osteogenesis imperfecta

Copy number variants in association with type 1 collagenopathy: Atypical osteogenesis imperfecta

PRDM15 loss of function links NOTCH and WNT/PCP signaling to patterning defects in holoprosencephaly

Eye Abnormalities in Patients With Chromosomal Disorders

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