Expanding the Genetic Landscape of Congenital Insensitivity to Pain
Issued Date
2026-02-01
Resource Type
eISSN
23767839
Scopus ID
2-s2.0-105029369626
Journal Title
Neurology Genetics
Volume
12
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Neurology Genetics Vol.12 No.1 (2026)
Suggested Citation
Pho-iam T., Kulsirichawaroj P., Likasitwattanakul S., Ridchuayrod N., Sanmaneechai O., Limwongse C., Zuchner S. Expanding the Genetic Landscape of Congenital Insensitivity to Pain. Neurology Genetics Vol.12 No.1 (2026). doi:10.1212/NXG.0000000000200346 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/115000
Title
Expanding the Genetic Landscape of Congenital Insensitivity to Pain
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Abstract
Objectives – Congenital insensitivity to pain (CIP) is a rare sensory neuropathy marked by absent nociception that predisposes patients to injuries and complications. Variants in genes, particularly PRDM12, underlie the condition. We investigated the molecular basis of CIP in 2 unrelated families.Methods – Trio whole-exome sequencing was performed for 3 CIP patients from 2 unrelated families and their parents; 1 family with negative results subsequently underwent whole genome sequencing. Sanger sequencing and fluorescent PCR confirmed and sized a GCC repeat expansion.Results – PRDM12 variants explained CIP in both families, each manifesting infantile-onset neuropathic keratopathy and self-mutilation. In Family 1, 2 siblings born to consanguineous parents were homozygous for a 19-GCC repeat expansion in the last exon, resulting in a polyalanine tract of 20 alanines—the largest PRDM12 polyalanine expansion reported to date. In Family 2, the proband carried 2 compound-heterozygous variants c.570+2T > G and c.796A > C (p.Thr266Pro) classified as pathogenic and likely pathogenic, respectively, and both previously undescribed.Discussion – These data broaden the genetic spectrum of CIP and reinforce PRDM12 as a key gene in pain perception. They also emphasize that diagnostic analysis should target both single-nucleotide variants and polyalanine expansions, which are often underrepresented in whole-exome or whole-genome sequencing data.