AI Article Synopsis

  • The study focused on identifying (epi)genetic factors in children born small for gestational age (SGA) experiencing undiagnosed syndromic short stature, involving 29 selected cases from a syndromic SGA cohort.
  • Advanced genetic analysis techniques like chromosomal microarray and whole exome sequencing were used, leading to the detection of pathogenic variants and uniparental disomy in several patients.
  • The findings revealed a 55.2% diagnosis rate, introduced 15 rare syndromes linked to SGA, and identified novel genes and copy number variants (CNVs), highlighting the complexity and diversity of syndromic short stature.

Article Abstract

Intrauterine onset syndromic short stature constitutes a group of diseases that pose challenges in differential diagnosis due to their rarity and clinical as well as molecular heterogeneity. The aim of this study was to investigate the presence of (epi)genetic causes in children born small for gestational age (SGA) and manifesting clinically undiagnosed syndromic short stature. The study group comprised twenty-nine cases selected from the syndromic SGA cohort. Various analyses were performed, including chromosomal microarray (CMA), methylation-specific-multiple ligation probe amplification for chromosomes 6,14 and 20, and whole exome sequencing (WES). Pathogenic copy number variants (CNVs) on chromosomes 2q13, 22q11.3, Xp22.33, 17q21.31, 19p13.13 and 4p16.31 causing syndromic growth disturbance were detected in six patients. Maternal uniparental disomy 14 was identified in a patient. WES was performed in the remaining 22 patients, revealing pathogenic variants in nine cases; six were monoallelic (ACAN, ARID2, NIPBL, PIK3R1, SMAD4, BRIP1), two were biallelic (BRCA2, RFWD3) and one was hemizygous (HUWE1). Seven of these were novel. Craniofacial dysmorphism, which is an important clue for the diagnosis of syndromes, was very mild in all patients. This study unveiled, for the first time, that ARID2 mutatios can cause syndromic SGA. In conclusion, a high (55.2%) diagnosis rate was achieved through the utilization of CMA, epigenetic and WES analyzes; 15 rare syndromes were defined, who were born with SGA and had atypical and/or mild dysmorphic findings. This study not only drew attention to the association of some rare syndromes with SGA, but also introduced novel genes and CNVs as potential contributors to syndromic SGA.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejmg.2023.104854DOI Listing

Publication Analysis

Top Keywords

syndromic short
12
syndromic sga
12
children born
8
born small
8
small gestational
8
gestational age
8
short stature
8
rare syndromes
8
syndromic
7
sga
6

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!