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

Mi, Jingyi; Parthasarathy, Padmini; Halliday, Benjamin J.; Morgan, Tim; Dean, John; Nowaczyk, Małgorzata J.M.; Markie, David; Robertson, Stephen; Wade, Emma M.

doi:10.3390/genes11121439

Cited by 8 publications

(14 citation statements)

References 16 publications

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“…Genomic DNA was extracted from whole blood and genome sequencing was carried out on individual III.6, by the Kinghorn Centre for Clinical Genomics (Sydney, Australia) using the HiSeq2500 (Illumina, CA, USA) as described previously [ 14 ]. Briefly, DNA was prepared with the Illumina 30× GS (TruSeq Nano) v2.5 kit.…”

Section: Methodsmentioning

confidence: 99%

Deletion of the last two exons of FGF10 in a family with LADD syndrome and pulmonary acinar hypoplasia

Wade

Parthasarathy

et al. 2021

Eur J Hum Genet

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Pulmonary acinar hypoplasia (PAH) and lacrimo-auriculo-dento-digital (LADD) syndrome have both been associated with loss-of-function variants in, or deletions of FGF10 . Here we report a multi-generational family with seven members manifesting varying features of LADD syndrome, with one individual dying in early infancy of PAH. Whole genome sequencing in one family member identified a 12,158 bp deletion on chromosome 5p12 that removes two of the three exons of FGF10 . Allele-specific PCR demonstrated that all affected family members, including the individual with PAH, carried the 12 kb deletion. We conclude the deletion is pathogenic and expands the mutational spectrum of FGF10 variants in LADD syndrome. The common mechanism underlying the variable clinical features of LADD syndrome is defective terminal branching of salivary and lacrimal glands and pulmonary acini, regulated by the TBX4-FGF10-FGFR2 pathway. The variable phenotypic expressivity of FGF10 haploinsufficiency from relatively benign to lethal is likely due to variation at other genetic loci.

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Section: Methodsmentioning

confidence: 99%

Deletion of the last two exons of FGF10 in a family with LADD syndrome and pulmonary acinar hypoplasia

Wade

Parthasarathy

et al. 2021

Eur J Hum Genet

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“…This 7-year-old female was born to nonconsanguineous English parents. This patient was recently published by Mi et al (2020). She presented prenatally with polyhydramnios and an abnormal anatomy scan…”

Section: Patientmentioning

confidence: 96%

“…Note: Consent was not obtained to publish images of Patient 11. Patient 4 recently reported inMi et al (2020). Patient 9 was previously published byChénier et al (2012)…”

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confidence: 99%

The phenotypic spectrum of AMER1‐related osteopathia striata with cranial sclerosis: The first Canadian cohort

Heikoop

Brick

Chitayat

et al. 2021

American J of Med Genetics Pt A

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Osteopathia striata with cranial sclerosis (OSCS; OMIM# 300373) is a rare X-linked disorder caused by mutations of the AMER1 gene. OSCS is traditionally considered a skeletal dysplasia, characterized by cranial sclerosis and longitudinal striations in the long bone metaphyses. However, OSCS affects many body systems and varies significantly in phenotypic severity between individuals. This case series focuses on the phenotypic presentation and development of individuals with OSCS. We provide an account of 12 patients with OSCS, ranging from 5 months to 38 years of age. These patients were diagnosed with OSCS after genetic testing confirmed pathogenic mutations in AMER1. Patient consent was obtained for photos and participation.Data were collected regarding perinatal history, dysmorphic features, and review of systems. This case series documents common facial dysmorphology, as well as rare extraskeletal features of OSCS, including two patients with intestinal malrotation and two patients with pyloric stenosis. We share four apparently nonmosaic males with OSCS (one de novo and three maternal variants). We also provide a clinical update on a patient who was previously published by Chénier et al. (2012). American Journal of Medical Genetics Part A, 158, 2946-2952. More research is needed to investigate the links between genotype and phenotype and assess the long-term comorbidities and overall quality of life of individuals with OSCS.

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“…Whole genome sequencing (WGS) was performed on DNA from the affected individuals and analyzed for SNV/indels and larger structural variants as previously described [ 11 ]. Briefly, DNA libraries were prepared using the TruSeq Nano DNA Library Prep kit v2.5 (Illumina, San Diego, CA, USA) to generate paired-end 150 base pair (bp) reads.…”

Section: Methodsmentioning

confidence: 99%

Intragenic Deletions in FLNB Are Part of the Mutational Spectrum Causing Spondylocarpotarsal Synostosis Syndrome

Fukushima

Parthasarathy

Wade

et al. 2021

Genes

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Spondylocarpotarsal synostosis syndrome (SCT) is characterized by vertebral fusions, a disproportionately short stature, and synostosis of carpal and tarsal bones. Pathogenic variants in FLNB, MYH3, and possibly in RFLNA, have been reported to be responsible for this condition. Here, we present two unrelated individuals presenting with features typical of SCT in which Sanger sequencing combined with whole genome sequencing identified novel, homozygous intragenic deletions in FLNB (c.1346-1372_1941+389del and c.3127-353_4223-1836del). Both deletions remove several consecutive exons and are predicted to result in a frameshift. To our knowledge, this is the first time that large structural variants in FLNB have been reported in SCT, and thus our findings add to the classes of variation that can lead to this disorder. These cases highlight the need for copy number sensitive methods to be utilized in order to be comprehensive in the search for a molecular diagnosis in individuals with a clinical diagnosis of SCT.

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

Cited by 8 publications

References 16 publications

Deletion of the last two exons of FGF10 in a family with LADD syndrome and pulmonary acinar hypoplasia

Deletion of the last two exons of FGF10 in a family with LADD syndrome and pulmonary acinar hypoplasia

The phenotypic spectrum of AMER1‐related osteopathia striata with cranial sclerosis: The first Canadian cohort

Intragenic Deletions in FLNB Are Part of the Mutational Spectrum Causing Spondylocarpotarsal Synostosis Syndrome

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