A familial case of overgrowth syndrome caused by a 9q22.3 microdeletion in a mother and daughter

Yamada, Hikari; Shimura, Masaru; Takahashi, Hidekuni; Nara, Shonosuke; Morishima, Yasuyuki; Go, Soken; Miyashita, Toshiyuki; Numabe, Hironao; Kawashima, Hisashi

doi:10.1016/j.ejmg.2020.103872

Cited by 3 publications

(5 citation statements)

References 15 publications

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“…Among the 9q22.3 microdeletion patients with overgrowth and/or macrosomia, a 550 Kb region encompassing PTCH1, C9orf3, FANCC, and five miRNAs has been reported to be the most frequently deleted common region (Yamada et al, 2020). This region was also deleted in our Patient 1 with 9q22.3 microdeletion syndrome.…”

Section: Microdeletion Syndromesmentioning

confidence: 49%

“…Prenatal‐onset overgrowth was reported in 20% of patients with 9q22.3 microdeletion syndrome, characterized by developmental delay and basal cell nevus (Gorlin) syndrome symptoms (Muller et al, 2012). Among the 9q22.3 microdeletion patients with overgrowth and/or macrosomia, a 550 Kb region encompassing PTCH1, C9orf3, FANCC , and five miRNAs has been reported to be the most frequently deleted common region (Yamada et al, 2020). This region was also deleted in our Patient 1 with 9q22.3 microdeletion syndrome.…”

Section: Discussionmentioning

confidence: 99%

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An investigation of the etiology and follow‐up findings in 35 children with overgrowth syndromes, including biallelic SUZ12 variant

Ülker

Alkaya

Çağlayan

et al. 2023

American J of Med Genetics Pt A

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Overgrowth-intellectual disability (OGID) syndromes are clinically and genetically heterogeneous group of disorders. The aim of this study was to examine the molecular etiology and long-term follow-up findings of Turkish OGID cohort. Thirty-five children with OGID were included in the study. Single gene sequencing, clinical exome analysis, chromosomal microarray analysis and whole exome sequencing were performed. Five pathogenic copy number variants were detected in the patients; three of them located on chromosome 5q35.2 (encompassing NSD1), others on 9q22.3 and 22q13.31. In 19 of 35 patients; we identified pathogenic variants in OGID genes associated with epigenetic regulation, NSD1 (n = 15), HIST1H1E (n = 1), SETD1B(n = 1), and SUZ12 (n = 2). The pathogenic variants in PIK3CA (n = 2), ABCC9 (n = 1), GPC4 (n = 2), FIBP (n = 1), and TMEM94 (n = 1) which had a role in other growth pathways were detected in seven patients. The diagnostic yield was 31/35(88%).Twelve pathogenic variants were novel. The common facial feature of the patients was prominent forehead. The patients with Sotos syndrome were observed to have milder intellectual disability than patients with other OGID syndromes. In conclusion, this study showed, for the first time, that biallelic variants of SUZ12 caused Imagawa-Matsumoto syndrome, monoallelic variants in SETDIB resulted in OGID. Besides expanded the phenotypes of very rare OGID syndromes caused by FIBP and TMEM94.

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Section: Microdeletion Syndromesmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

An investigation of the etiology and follow‐up findings in 35 children with overgrowth syndromes, including biallelic SUZ12 variant

Ülker

Alkaya

Çağlayan

et al. 2023

American J of Med Genetics Pt A

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“…PTCH1, ERCC6L2, LINC00476 , and FANCC are highly expressed in the osteosarcoma cell line SAOS‐2 undergoing mineralization (Supplementary Figures S4–S7), and dysregulation of these genes could contribute to the skeletal phenotype in this patient. Loci containing let‐7 family microRNAs are frequently within 9q22.3 deletions and have been implicated in aspects of the phenotype (Yamada et al, 2020) but these sequences, at around 9:94,220,000, are outside the deletion in the present patient. A recent article (Liu et al, 2020) showed that a sequence within the deletion (designated RP11‐43505.2 in the article, which maps close to MT1P1 and likely overlaps with FANCC‐203 ) is targeted by WNT signaling.…”

Section: Discussionmentioning

confidence: 67%

“…Therefore, it would be expected that loss of the paternal allele of an imprinted gene would expose the maternal allele and decrease growth, which is in contrast to the reported cases. Yamada and colleagues report a mother and daughter who both have a 4 Mb deletion of 9q22.3 (Yamada et al, 2020). The daughter, who inherited the deletion from her mother and therefore carries the paternal sequence in the deleted region, showed postnatal overgrowth.…”

Section: Discussionmentioning

confidence: 99%

“…Up to 13% of BCNS cases have deletions of at least one exon (Evans et al, 2017) and a small proportion of these have larger deletions of chromosome 9 encompassing PTCH1 as well as additional material. The longest reported such deletion to date is 20.5 mb while the shortest is 0.35 mb (Boonen et al, 2005; Brickler et al, 2014; Cajaiba et al, 2006; Cayrol et al, 2019; Garavelli et al, 2013; Isidor et al, 2013; Kieny et al, 2018; Muller et al, 2012; Redon et al, 2006; Reichert et al, 2015; Shimojima et al, 2009; Yamada et al, 2020). As with other microdeletion syndromes (Schmickel, 1986; Weise et al, 2012), most patients with 9q22.3 deletion have multiple signs and symptoms in addition to the manifestations of BCNS.…”

Section: Introductionmentioning

confidence: 99%

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Microdeletion of 9q22.3: A patient with minimal deletion size associated with a severe phenotype

Ewing

Cheetham

McGill

et al. 2021

American J of Med Genetics Pt A

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Basal cell nevus syndrome (also known as Gorlin Syndrome; MIM109400) is an autosomal dominant disorder characterized by recurrent pathological features such as basal cell carcinomas and odontogenic keratocysts as well as skeletal abnormalities. Most affected individuals have point mutations or small insertions or deletions within the PTCH1 gene on human chromosome 9, but there are some cases with more extensive deletion of the region, usually including the neighboring FANCC and/or ERCC6L2 genes. We report a 16‐year‐old patient with a deletion of approximately 400,000 bases which removes only PTCH1 and some non‐coding RNA genes but leaves FANCC and ERCC6L2 intact. In spite of the small amount of DNA for which he is haploid, his phenotype is more extreme than many individuals with longer deletions in the region. This includes early presentation with a large number of basal cell nevi and other skin lesions, multiple jaw keratocysts, and macrosomia. We found that the deletion was in the paternal chromosome, in common with other macrosomia cases. Using public databases, we have examined possible interactions between sequences within and outside the deletion and speculate that a regulatory relationship exists with flanking genes, which is unbalanced by the deletion, resulting in abnormal activation or repression of the target genes and hence the severity of the phenotype.

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Genomics of human congenital hydrocephalus

et al. 2021

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A familial case of overgrowth syndrome caused by a 9q22.3 microdeletion in a mother and daughter

Cited by 3 publications

References 15 publications

An investigation of the etiology and follow‐up findings in 35 children with overgrowth syndromes, including biallelic SUZ12 variant

An investigation of the etiology and follow‐up findings in 35 children with overgrowth syndromes, including biallelic SUZ12 variant

Microdeletion of 9q22.3: A patient with minimal deletion size associated with a severe phenotype

Genomics of human congenital hydrocephalus

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