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

AbstractOsteopathia striata with cranial sclerosis is an X-linked dominant bone dysplasia with osteosclerosis. It should be suspected in girls with macrocephaly, intellectual disability with unique facial dysmorphic features. We described the clinical and radiological profile of a patient with this rare disorder. A novel heterozygous variant was identified in the AMER1 gene which leads to premature truncation of the AMER1 protein. Facial gestalt recognition using artificial intelligence and radiographic features were used to narrow the differential diagnosis.

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Deletion of Exon 1 in AMER1 in Osteopathia Striata with Cranial Sclerosis

Genes ◽

10.3390/genes11121439 ◽

2020 ◽

Vol 11 (12) ◽

pp. 1439

Author(s):

Jingyi Mi ◽

Padmini Parthasarathy ◽

Benjamin J. Halliday ◽

Tim Morgan ◽

John Dean ◽

...

Keyword(s):

Genome Sequencing ◽

Severe Phenotype ◽

Gene Deletions ◽

Exon 2 ◽

Pathogenic Variants ◽

Osteopathia Striata ◽

Cranial Sclerosis ◽

Exon 1 ◽

Dominant Condition ◽

Dependent Probe

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 AMER1, 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 AMER1. Therefore, genome sequencing was employed which identified two deletions containing the non-coding exon 1 of AMER1 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.

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Cranial Sclerosis with Striated Bone Disease (Osteopathia Striata)

Klinische Pädiatrie ◽

10.1055/s-2008-1033900 ◽

1986 ◽

Vol 198 (05) ◽

pp. 418-424 ◽

Cited By ~ 12

Author(s):

H. Piechowiak ◽

F. Goebel ◽

U. Hirche ◽

R. Tyrell

Keyword(s):

Bone Disease ◽

Osteopathia Striata ◽

Cranial Sclerosis

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First female prenatal case of osteopathia striata with cranial sclerosis in a fetus carrying a de-novo 1.9 Mbp interstitial deletion at Xq11.1q11.2

Clinical Dysmorphology ◽

10.1097/mcd.0000000000000192 ◽

2017 ◽

Vol 26 (4) ◽

pp. 231-234

Author(s):

Marie-Laure Vuillaume ◽

Anna-Gaelle Valard ◽

Nada Houcinat ◽

Julie Bouron ◽

Cécile Boucher ◽

...

Keyword(s):

De Novo ◽

Interstitial Deletion ◽

Osteopathia Striata ◽

Cranial Sclerosis

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Prenatal Diagnosis of Osteopathia Striata with Cranial Sclerosis in a Male Fetus with a ~330kb Deletion of Xq11.1 Involving the WTX Gene

American Journal of Medical and Biological Research ◽

10.12691/ajmbr-1-1-6 ◽

2013 ◽

Vol 1 (1) ◽

pp. 33-36 ◽

Cited By ~ 2

Author(s):

Patrick L. Wilson ◽

Ashley Davis ◽

Jean Ricci Goodman ◽

Lauren Notley ◽

Shibo Li ◽

...

Keyword(s):

Prenatal Diagnosis ◽

Male Fetus ◽

Osteopathia Striata ◽

Cranial Sclerosis

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A novel contiguous gene deletion ofAVPR2andARHGAP4genes in male dizygotic twins with nephrogenic diabetes insipidus and intellectual disability

American Journal of Medical Genetics Part A ◽

10.1002/ajmg.a.35591 ◽

2012 ◽

Vol 158A (10) ◽

pp. 2511-2518 ◽

Cited By ~ 12

Author(s):

Lingli Huang ◽

Gemma Poke ◽

Jozef Gecz ◽

Kate Gibson

Keyword(s):

Intellectual Disability ◽

Diabetes Insipidus ◽

Nephrogenic Diabetes Insipidus ◽

Gene Deletion ◽

Dizygotic Twins ◽

Contiguous Gene

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Chromosome 16p13.3 Contiguous Gene Deletion Syndrome including the SLX4, DNASE1, TRAP1, and CREBBP Genes Presenting as a Relatively Mild Rubinstein–Taybi Syndrome Phenotype: A Case Report of a Saudi Boy

Case Reports in Genetics ◽

10.1155/2020/6143050 ◽

2020 ◽

Vol 2020 ◽

pp. 1-5

Author(s):

Mohammad M. Al-Qattan ◽

Zuhair A. Rahbeeni ◽

Zuhair N. Al-Hassnan ◽

Abdulaziz Jarman ◽

Atif Rafique ◽

...

Keyword(s):

Gene Deletion ◽

Deletion Syndrome ◽

Syndrome Type ◽

Partial Deletion ◽

Gene Deletions ◽

Mild Phenotype ◽

Contiguous Gene ◽

Chromosome 16P13.3 ◽

Contiguous Gene Deletion Syndrome

The classic Rubinstein–Taybi syndrome Type 1 (RSTS1, OMIM 180849) is caused by heterozygous mutations or deletions of the CREBBP gene. Herein, we describe the case of a Saudi boy with chromosome 16p13.3 contiguous gene deletion syndrome (OMIM 610543) including the SLX4, DNASE1, TRAP1, and CREBBP genes, but presenting with a relatively mild RSTS1 syndrome phenotype. Compared with previously reported cases with severe phenotypes associated with 16p13.3 contiguous gene deletions, our patient had partial deletion of the CREBBP gene (with a preserved 5′ region), which might explain his relatively mild phenotype.

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Whole Exome Sequencing Provides the Correct Diagnosis in a Case of Osteopathia Striata with Cranial Sclerosis: Case Report of a Novel Frameshift Mutation in AMER1

Journal of Pediatric Genetics ◽

10.1055/s-0040-1710058 ◽

2020 ◽

Author(s):

José María García-Aznar ◽

Noelia Ramírez ◽

David De Uña ◽

Elisa Santiago ◽

Lorenzo Monserrat

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Target Genes ◽

Correct Diagnosis ◽

Sotos Syndrome ◽

Pathogenic Variants ◽

Osteopathia Striata ◽

Whole Exome ◽

Cranial Sclerosis ◽

Extended Analysis

AbstractThe diagnosis of rare diseases with multisystem manifestations can constitute a difficult process that delays the determination of the underlying cause. Whole exome sequencing (WES) provides a suitable option to examine multiple target genes associated with several disorders that display common features. In this study, we report the case of a female patient suspected of having Sotos syndrome. Screening for the initially selected genes, considering Sotos syndrome and Sotos-like disorders, did not identify any pathogenic variants that could explain the phenotype. The extended analysis, which considered all genes in the exome associated with features consistent with those shown by the studied patient, revealed a novel frameshift variant in the AMER1 gene, responsible for osteopathia striata with cranial sclerosis. WES analysis and an updated revision of previously reported disease-causing mutations, proved useful to reach an accurate diagnosis and guide further examination to identify critical abnormalities.

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