A Novel Homozygous Frameshift Variant in DYM Causing Dyggve-Melchior-Clausen Syndrome in Pakistani Patients
| Autor: | Nagwa E. A. Gaboon, Asia Parveen, Khaled A. Ahmad, Taghreed Shuaib, Jumana Y. Al-Aama, Lereen Abdelwehab, Amina Arif, Naveed Wasif |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Dyggve-Melchior-Clausen syndrome
Smith-McCort dysplasia Microcephaly Sanger sequencing Case Report 030204 cardiovascular system & hematology DYM Pediatrics Frameshift mutation 03 medical and health sciences symbols.namesake 0302 clinical medicine Brain Abnormalities 030225 pediatrics Intellectual disability Medicine ddc:610 Genanalyse Genetics Spondyloepimetaphyseal dysplasia business.industry Coarse facial features lcsh:RJ1-570 Musculoskeletal abnormalities lcsh:Pediatrics Sequence analysis DNA Smith McCort dysplasia medicine.disease consanguineous Dysplasia Pediatrics Perinatology and Child Health symbols business Erbkrankheit |
| Zdroj: | Frontiers in Pediatrics, Vol 8 (2020) Frontiers in Pediatrics |
| ISSN: | 2296-2360 |
| DOI: | 10.3389/fped.2020.00383/full |
| Popis: | Background: Dyggve-Melchior-Clausen syndrome (DMC) is a skeletal dysplasia with associated defects of brain development and intelligence. The truncating pathogenic variants in DYM are the most frequent cause of DMC. Smith-McCort (SMC), another skeletal dysplasia, is also caused by non-synonymous DYM variants. Methods and Results: In the current study, we examined a Pakistani consanguineous family with three affected members. Clinical features like spondyloepimetaphyseal dysplasia, indicative of characteristic skeletal abnormalities, and intellectual disability were observed. Our male patients had microcephaly and coarse facial features while the female patient did not represent microcephaly or abnormal facies, which are significant features of DMC patients. Sanger sequencing identified a novel homozygous frameshift insertion (c.95_96insT, p.W33Lfs*14) in DYM, which likely leads to nonsense-mediated decay (NMD). Conclusion: The novel frameshift change verifies the fact that pathogenic variants in DYM are the most frequent cause of DMC. |
| Databáze: | OpenAIRE |
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