Diagnosis of 9q22.3 microdeletion syndrome in utero following identification of craniosynostosis, overgrowth, and skeletal anomalies

Reichert, Sara Chadwick; Zelley, Kristin; Nichols, Kim E.; Eberhard, Moriah; Zackai, Elaine H.; Martinez-Poyer, Juan

doi:10.1002/ajmg.a.37013

Cited by 12 publications

(8 citation statements)

References 10 publications

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“…It is a contiguous gene deletion syndrome, and the main genes involved in the condition are PTCH1 and FANCC (MIM * 613899). The clinical manifestations are similar to those of BCNS; additional features that can be found in the syndrome, and not in BCNS are: metopic craniosynostosis, obstructive hydrocephalus, macrosomia, and intellectual disability (Muller et al, ; Reichert et al, ).…”

Section: Introductionmentioning

confidence: 89%

Unexpected phenotype in a frameshift mutation of PTCH1

Beltrami

Prada

Tolva

et al. 2019

Molec Gen & Gen Med

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Background Gorlin syndrome, also known as basal cell nevus syndrome (BCNS), is a rare autosomal dominant genetic condition, characterized by the presence of multiple basal cell carcinomas at a young age, odontogenic keratocysts, skeletal anomalies, macrocephaly, and dysmorphisms. BCNS is mainly caused by mutations in PTCH1, an onco‐suppressor gene that maps at 9q22.3 region. A disease related to BCNS is the 9q22.3 microdeletion syndrome. This condition has an overlapping clinical phenotype with the BCNS, but it can present in addition: metopic craniosynostosis, overgrowth, obstructive hydrocephalus, developmental delay, intellectual disability, and seizures. This syndrome is caused by the deletion of a genomic region containing the PTCH1 and the FANCC. Methods and Results We report the case of an 11‐year‐old girl that came to our attention for overgrowth, dysmorphic features of the face, and craniosynostosis, but with a normal intellectual and motor development. At first we performed an array‐comparative genomic hybridization (aCGH) analysis. The analysis showed no copy number changes. Then, we performed the analysis of the PTCH1 by next‐generation sequencing. This analysis showed a heterozygous frameshift mutation. Conclusion This is the first case with a PTCH1 point mutation with a 9q22.3 microdeletion syndrome phenotype. This finding may strengthen the importance of the role of the PTCH1, especially regarding the metopic craniosynostosis.

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Section: Introductionmentioning

confidence: 89%

Unexpected phenotype in a frameshift mutation of PTCH1

Beltrami

Prada

Tolva

et al. 2019

Molec Gen & Gen Med

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“…Two SNPs of interest are located on the gene FANCC , which encodes a DNA repair protein with a role in the maintenance of normal chromosome stability. FANCC is implicated in Gorlin syndrome that has a phenotype including broad nasal root, cleft lip, and cleft palate (Reichert et al, 2015). FANCC is also linked to Fanconi anemia that has a phenotype including craniosynostosis, microencephaly and small eyes (de Winter et al, 2000).…”

Section: Resultsmentioning

confidence: 99%

Associations Between Genetic Data and Quantitative Assessment of Normal Facial Asymmetry

2018

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Human facial asymmetry is due to a complex interaction of genetic and environmental factors. To identify genetic influences on facial asymmetry, we developed a method for automated scoring that summarizes local morphology features and their spatial distribution. A genome-wide association study using asymmetry scores from two local symmetry features was conducted and significant genetic associations were identified for one asymmetry feature, including genes thought to play a role in craniofacial disorders and development: NFATC1, SOX5, NBAS, and TCF7L1. These results provide evidence that normal variation in facial asymmetry may be impacted by common genetic variants and further motivate the development of automated summaries of complex phenotypes.

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“…Twenty-eight cases of interstitial 9q deletions were found span, flanked, or partially overlapped with the current case's deletion. [8][9][10][22][23][24][25][26][27][28][29][30][31][32][33][34] The clinical features of individuals with deletion of 9q varied with few common features.…”

Section: Discussionmentioning

confidence: 99%

De Novo Interstitial Deletion of 9q in a Pediatric Patient With Global Developmental Delay

Keselman

Singh

Cohen

et al. 2019

Child Neurology Open

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Cytogenomic microarray (CMA) methodologies, including array comparative genomic hybridization (aCGH) and single-nucleotide polymorphism-detecting arrays (SNP-array), are recommended as the first-tier test for the evaluation of imbalances associated with intellectual disability, autism, and multiple congenital anomalies. The authors report on a child with global developmental delay (GDD) and a de novo interstitial 7.0 Mb deletion of 9q21.33q22.31 detected by aCGH. The patient that the authors report here is noteworthy in that she presented with GDD and her interstitial deletion is not inclusive of the 9q22.32 locus that includes the PTCH1 gene, which is implicated in Gorlin syndrome, or basal cell nevus syndrome (BCNS), has not been previously reported among patients with a similar or smaller size of the deletion in this locus suggesting that the genomic contents in the identified deletion on 9q21.33q22.31 is critical for the phenotype.

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Diagnosis of 9q22.3 microdeletion syndrome in utero following identification of craniosynostosis, overgrowth, and skeletal anomalies

Cited by 12 publications

References 10 publications

Unexpected phenotype in a frameshift mutation of PTCH1

Unexpected phenotype in a frameshift mutation of PTCH1

Associations Between Genetic Data and Quantitative Assessment of Normal Facial Asymmetry

De Novo Interstitial Deletion of 9q in a Pediatric Patient With Global Developmental Delay

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