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Use of Expanded Carrier Screening for Retrospective Diagnosis of Two Deceased Siblings With Van Maldergem Syndrome 2: Case Report Publisher



Rahmani N1 ; Ahmadvand M2 ; Khakpour G1, 3
Authors
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Authors Affiliations
  1. 1. Department of Medical Genetics and Molecular Biology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Oncology and Stem Cell Transplantation, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Department of Eye Research Center, The Five Senses Institute, Rassoul Akram Hospital, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

Source: Asian Biomedicine Published:2022


Abstract

Van Maldergem syndrome (VMLDS) is a recessive disease which affects multiple organs including the face, ear, and limb extremities. It can be caused by pathogenic variants in either the gene DCHS1 or FAT4. Diagnosis of VMLDS is complicated, especially regarding its similarity of symptoms to Hennekam syndrome, another disorder caused by FAT4 variants. Reported patients are two infantile siblings with multiple congenital anomalies, who deceased without clinical diagnosis. Whole exome sequencing was exploited for expanded carrier screening (ECS) of their parents, which revealed a novel splicing variant in the gene FAT4, NM_024582.6: c.7018+1G>A. In silico analysis of the variant indicates loss of canonical donor splice site of intron 6. This variant is classified as pathogenic based on ACMG criteria. Reverse phenotyping of patients resulted in likely diagnosis of VMLDS2. This study reaffirms the possibility of using ECS, leading to the genetic diagnosis of a rare disease with complicated clinical features. © 2023 Nasim Rahmani et al., published by Sciendo.
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