Deletion of Exon 1 in in Osteopathia Striata with Cranial Sclerosis.

Genes (Basel) 2020 Nov 30;11(12). Epub 2020 Nov 30.

Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin 9016, New Zealand.

Osteopathia striata with cranial sclerosis (OSCS) is an X-linked dominant condition characterised by metaphyseal striations, macrocephaly, cleft palate, and developmental delay in affected females. Males have a more severe phenotype with multi-organ malformations, and rarely survive. To date, only frameshift and nonsense variants in exon 2, the single coding exon of , or whole gene deletions have been reported to cause OSCS. In this study, we describe two families with phenotypic features typical of OSCS. Exome sequencing and multiplex ligation-dependent probe amplification (MLPA) did not identify pathogenic variants in . Therefore, genome sequencing was employed which identified two deletions containing the non-coding exon 1 of in the families. These families highlight the importance of considering variants or deletions of upstream non-coding exons in conditions such as OSCS, noting that often such exons are not captured on probe or enrichment-based platforms because of their high G/C content.

Download full-text PDF

Source
http://dx.doi.org/10.3390/genes11121439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760256PMC
November 2020

Publication Analysis

Top Keywords

cranial sclerosis
8
osteopathia striata
8
striata cranial
8
sequencing multiplex
4
multiplex ligation-dependent
4
exome sequencing
4
oscs exome
4
typical oscs
4
ligation-dependent probe
4
variants genome
4
pathogenic variants
4
mlpa identify
4
amplification mlpa
4
features typical
4
probe amplification
4
identify pathogenic
4
families phenotypic
4
coding exon
4
exon gene
4
single coding
4

Similar Publications

Male child with somatic mosaic Osteopathia Striata with Cranial Sclerosis caused by a novel pathogenic AMER1 frameshift mutation.

Am J Med Genet A 2017 Jul 12;173(7):1931-1935. Epub 2017 May 12.

Department of Clinical Genetics, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.

Osteopathia striata with cranial sclerosis (OSCS; OMIM #300373) is a rare X-linked dominant condition caused by mutations in the AMER1 gene (also known as WTX or FAM123B). It is a condition which usually affects females in whom the clinical phenotype can be extremely variable. Conversely affected males typically die in utero or during the neonatal period [Perdu et al. Read More

View Article and Full-Text PDF
July 2017

Wilms tumor in patients with osteopathia striata with cranial sclerosis.

Eur J Hum Genet 2020 Sep 2. Epub 2020 Sep 2.

Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago, Dunedin, 9016, New Zealand.

Germline pathogenic variants in AMER1 cause osteopathia striata with cranial sclerosis (OSCS: OMIM 300373), an X-linked sclerosing bone disorder. Female heterozygotes exhibit metaphyseal striations in long bones, macrocephaly, cleft palate, and, occasionally, learning disability. Male hemizygotes typically manifest the condition as fetal or neonatal death. Read More

View Article and Full-Text PDF
September 2020

A novel WTX mutation in a female patient with osteopathia striata with cranial sclerosis and hepatoblastoma.

Am J Med Genet A 2014 Apr 23;164A(4):998-1002. Epub 2014 Jan 23.

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Osteopathia striata with cranial sclerosis (OSCS) is an X-linked dominant sclerosing bone dysplasia. Typically affected females show macrocephaly, characteristic facial appearance, cleft palate, mild learning difficulties, hearing loss, sclerosis of the long bones and skull, and longitudinal striations visible on radiographs of the long bones, pelvis and scapulae. Typically affected males usually die at the fetal or early neonatal stage. Read More

View Article and Full-Text PDF
April 2014

Osteopathia striata congenita with cranial sclerosis and intellectual disability due to contiguous gene deletions involving the WTX locus.

Clin Genet 2013 Mar 5;83(3):251-6. Epub 2012 Jul 5.

Department of Paediatrics, Dunedin School of Medicine, Otago University, Dunedin, New Zealand.

Osteopathia striata congenita with cranial sclerosis (OSCS) is a skeletal dysplasia caused by germline deletions of or truncating point mutations in the X-linked gene WTX (FAM123B, AMER1). Females present with longitudinal striations of sclerotic bone along the long axis of long bones and cranial sclerosis, with a high prevalence of cleft palate and hearing loss. Intellectual disability or neurodevelopmental delay is not observed in females with point mutations in WTX leading to OSCS. Read More

View Article and Full-Text PDF
March 2013