A Novel Homozygous Frameshift Variant in DYM Causing Dyggve-Melchior-Clausen Syndrome in Pakistani Patients.

Autor:	Gaboon NEA; Faculty of Medicine, Medical Genetics Center, Ain Shams University, Cairo, Egypt., Parveen A; Center for Research in Molecular Medicine (CRiMM), Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, Pakistan.; Faculty of Life Sciences, University of Central Punjab (UCP), Lahore, Pakistan., Ahmad KA; Department of Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt., Shuaib T; Pediatric Department, King Abdulaziz University, Jeddah, Saudi Arabia., Al-Aama JY; Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.; Princess Al-Jawhara Albrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia., Abdelwehab L; Faculty of Medicine, Ain Shams University, Cairo, Egypt., Arif A; Faculty of Life Sciences, University of Central Punjab (UCP), Lahore, Pakistan., Wasif N; Center for Research in Molecular Medicine (CRiMM), Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, Lahore, Pakistan.; Institute of Human Genetics, University of Ulm and University of Ulm Medical Center, Ulm, Germany.; Institute of Human Genetics, University Hospital Schleswig-Holstein, Kiel, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in pediatrics [Front Pediatr] 2020 Jul 16; Vol. 8, pp. 383. Date of Electronic Publication: 2020 Jul 16 (Print Publication: 2020).
DOI:	10.3389/fped.2020.00383
Abstrakt:	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. (Copyright © 2020 Gaboon, Parveen, Ahmad, Shuaib, Al-Aama, Abdelwehab, Arif and Wasif.)
Databáze:	MEDLINE
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