• Azadeh Reshadmanesh, Shima Dehdahsi, Fatemeh Ahangari, Kimia Kahrizi, Ariana Kariminejad, Shokouh Sadat Mahdavi, Saeed Talebi, and Hossein Najmabadi.
• Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
• Arch Iran Med. 2024 Dec 1; 27 (12): 700706700-706.

AbstractHere, we report a case with concomitant variants: a novel homozygous HERC1 gene variant and a novel heterozygous PMP22 duplication. The 2-year-old male presented with seizures, developmental delay, macrocephaly, hypotonia, unilateral hypertrophy, thoracic scoliosis, normal brain MRI, and elevated homocysteine level which normalized after treatment. Whole exome sequencing (WES) revealed a co-occurrence of a homozygous novel likely pathogenic variant in the HERC1 gene (NM_003922.3:c.1280dup (p.ILe469Aspfs*33) and a novel heterozygous large duplication of exon 1-5 in the PMP22 gene, which has not been reported previously. The case underscores the challenges in understanding genotype-phenotype correlations and suggests a potential interplay between these genetic variants in shaping the current and future clinical phenotype of the patient. In the case of genetic diseases, this event may have important implications on family members' counseling, and concomitant variants in Charcot-Marie-Tooth (CMT) families should be considered when significant intra-familial clinical heterogeneity is observed.© 2024 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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