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The Identification of Two Pathogenic Variants in a Family With Mild and Severe Forms of Developmental Delay Publisher Pubmed



Miyake N1 ; Heydari S2 ; Garshasbi M2 ; Saitoh S3 ; Nasiri J4 ; Hamanaka K1 ; Takata A1 ; Matsumoto N1 ; Beheshti FH4 ; Chaleshtori ARS2
Authors
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Authors Affiliations
  1. 1. Yokohama City University Graduate School of Medicine, Yokohama, 236-0004, Japan
  2. 2. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box, Tehran, 14115-331, Iran
  3. 3. Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan
  4. 4. Department of Pediatric Neurology, Child Growth and Development Research Center & Research Institute for Primordial Prevention of Non-communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Journal of Human Genetics Published:2021


Abstract

Intellectual disability (ID) accounts for 1% of the general population, and it is caused by the interplay between the genetic and/or environmental factors. The genetic components responsible for the development of ID are highly heterogeneous, and the phenotype and severity of the disease vary in patients even if they have an identical pathological variant and/or belong to the same family. Herein, we reported two male siblings with ID in an Iranian family. By means of the whole-exome sequencing method, elder brother affected by a moderate form of ID exhibited a de novo missense variant in the KCNQ3 gene, while another sibling afflicted with a severe form of the disease exhibited a de novo in-frame deletion in the UBE3A gene. Both variants have been previously ascribed to similar clinical phenotypes. In addition, a genetic variant in the KCNQ3 gene was transmitted to his son, who had a mild form of ID. To our knowledge, all individuals with KCNQ3-related developmental delay show de novo variants in the KCNQ3 gene. Thus, this familial case exhibit milder phenotype that might extend the clinical spectrum of KCNQ3 pathogenic variants. In addition, the current report highlights the significance of the clinical evaluation and non-biased assessment of the genetic analysis. © 2020, The Author(s), under exclusive licence to The Japan Society of Human Genetics.
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