Expanding the Clinical and Molecular Spectrum of Cartilage-Hair Hypoplasia in the Mexican Population
5 affiliations
- 1División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Sierra Mojada 800, Independencia Oriente, Guadalajara 44340, Jalisco, Mexico
- 2Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, University of Guadalajara (UdeG), Sierra Mojada 950, Independencia Oriente, Guadalajara 44340, Jalisco, Mexico
- 3UMAE Hospital de Pediatría del Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, Av. Belisario Domínguez 735, La Perla, Guadalajara 44360, Jalisco, Mexico
- 4Center for Registry and Research in Congenital Anomalies (CRIAC), Service of Genetics and Cytogenetics Unit—‘Dr. Enrique Corona-Rivera’ Institute of Human Genetics, ‘Dr. Juan I. Menchaca’ Civil Hospital of Guadalajara (HCG), Guadalajara 44340, Jalisco, Mexico
- 5Health Sciences University Center (CRIAC HCG—UdeG), University of Guadalajara (UdeG), Guadalajara 44340, Jalisco, Mexico
Abstract
Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive skeletal dysplasia caused by variants in RMRP (RNA component of mitochondrial RNA processing endoribonuclease), which encodes a non-coding RNA. Despite its well-established clinical and molecular spectrum in some populations, data from Mexico remain limited. We report eight patients from seven unrelated families with CHH. Clinical and radiographic findings were assessed, and RMRP was analyzed by polymerase chain reaction and Sanger sequencing. All patients exhibited disproportionate short stature; prenatal long-bone shortening and short stature at birth occurred in 50%. Radiographs showed widened long bones and metaphyseal dysplasia in all patients. Extraskeletal manifestations were observed in four patients, each with a distinct feature: immunodeficiency, anemia, Hirschsprung disease, or lymphopenia. RMRP variants were identified in all patients, comprising two homozygous and six compound heterozygous genotypes. Eight variants were detected: three pathogenic (n.6C>T, n.147G>A, and n.72A>G), two likely pathogenic (n.127C>T and n.125C>T), two variants of uncertain significance (n.128G>C and n.215C>T), and a novel promoter deletion (n.-39_-19del) encompassing the RMRP TATA box, classified as likely pathogenic according to the ClinGen RMRP variant interpretation specifications (GN088, Version 1.3). This study expands the clinical and molecular spectrum of CHH in the Mexican population and provides additional evidence for RMRP variant interpretation.
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BibTeX
@article{roblesespinoza2026expanding,
title = {{Expanding the Clinical and Molecular Spectrum of Cartilage-Hair Hypoplasia in the Mexican Population}},
author = {Kiabeth Robles-Espinoza and Eduardo Esparza-García and Jorge Román Corona-Rivera and Mariana Pérez-Coria and Perla Graciela Rodríguez-Gutiérrez and Juan Ramón González García and María Teresa Magaña-Torres},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27198815},
url = {https://www.mdpi.com/1422-0067/27/19/8815},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Expanding the Clinical and Molecular Spectrum of Cartilage-Hair Hypoplasia in the Mexican Population
AU - Kiabeth Robles-Espinoza
AU - Eduardo Esparza-García
AU - Jorge Román Corona-Rivera
AU - Mariana Pérez-Coria
AU - Perla Graciela Rodríguez-Gutiérrez
AU - Juan Ramón González García
AU - María Teresa Magaña-Torres
PY - 2026
DA - 2026/10/02
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27198815
UR - https://www.mdpi.com/1422-0067/27/19/8815
AB - Cartilage-hair hypoplasia (CHH) is a rare autosomal recessive skeletal dysplasia caused by variants in RMRP (RNA component of mitochondrial RNA processing endoribonuclease), which encodes a non-coding RNA. Despite its well-established clinical and molecular spectrum in some populations, data from Mexico remain limited. We report eight patients from seven unrelated families with CHH. Clinical and radiographic findings were assessed, and RMRP was analyzed by polymerase chain reaction and Sanger sequencing. All patients exhibited disproportionate short stature; prenatal long-bone shortening and short stature at birth occurred in 50%. Radiographs showed widened long bones and metaphyseal dysplasia in all patients. Extraskeletal manifestations were observed in four patients, each with a distinct feature: immunodeficiency, anemia, Hirschsprung disease, or lymphopenia. RMRP variants were identified in all patients, comprising two homozygous and six compound heterozygous genotypes. Eight variants were detected: three pathogenic (n.6C>T, n.147G>A, and n.72A>G), two likely pathogenic (n.127C>T and n.125C>T), two variants of uncertain significance (n.128G>C and n.215C>T), and a novel promoter deletion (n.-39_-19del) encompassing the RMRP TATA box, classified as likely pathogenic according to the ClinGen RMRP variant interpretation specifications (GN088, Version 1.3). This study expands the clinical and molecular spectrum of CHH in the Mexican population and provides additional evidence for RMRP variant interpretation.
SN - 1422-0067
ER -