Deletion of the last two exons of FGF10 in a family with LADD syndrome and pulmonary acinar hypoplasia
| Autor: | Stephen P. Robertson, Tim Cundy, Jingyi Mi, Bernd Wollnik, Timothy R. Morgan, Padmini Parthasarathy, Emma M. Wade |
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| Rok vydání: | 2021 |
| Předmět: |
Biology
Brief Communication 03 medical and health sciences Exon Genetics research Genetics medicine Humans Abnormalities Multiple Expressivity (genetics) Hearing Loss Genetics (clinical) Whole genome sequencing 0303 health sciences Respiratory tract diseases FGF10 Lacrimal Apparatus Diseases Tooth Abnormalities 030305 genetics & heredity Chromosome Exons medicine.disease Phenotype Hypoplasia stomatognathic diseases Syndactyly Haploinsufficiency Fibroblast Growth Factor 10 |
| Zdroj: | European Journal of Human Genetics |
| ISSN: | 1476-5438 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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