Meier-Gorlin syndrome due to a recurrent DONSON variant in a Turkish family: first report of thumb aplasia and long-term growth data
Journal of Pediatric Endocrinology and Metabolism, cilt.39, sa.4, ss.388-395, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 39 Sayı: 4
- Basım Tarihi: 2026
- Doi Numarası: 10.1515/jpem-2025-0470
- Dergi Adı: Journal of Pediatric Endocrinology and Metabolism
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE, Health Research Premium Collection (ProQuest)
- Sayfa Sayıları: ss.388-395
- Anahtar Kelimeler: primordial dwarfism, Meier-Gorlin syndrome, DONSON, founder effect, thumb aplasia
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Objectives: Meier-Gorlin syndrome (MGORS) is a rare primordial dwarfism characterized by microtia, patellar hypoplasia/aplasia, and short stature. Additional features may include skeletal, respiratory, urogenital, and endocrine abnormalities. 13 genes have been implicated, with DONSON, essential for replication fork stability and intra-S phase checkpoint activation, being the most recently identified. Only six patients with DONSON-related MGORS have been reported. This study expands the phenotype by presenting long-term follow-up and prenatal data in two affected siblings. Case presentation: The index patient, a 10-year-old male, had short stature, microcephaly, microtia, craniofacial features, hearing loss, patellar aplasia, and genitourinary anomalies. Despite an early growth delay, his height progressively improved without intervention. Whole-exome sequencing revealed a homozygous pathogenic c.631C>T p.(Arg211Cys) variant in DONSON (NM_017613.3). Following genetic counseling, the family declined prenatal testing in a subsequent pregnancy complicated by intrauterine growth restriction. The newborn female sibling carried the same variant and displayed DONSON-related MGORS features, including the first reported case of thumb aplasia. Additional findings in the family included renal hypoplasia, 2-4 toe syndactyly, and hypospadias. Conclusions: This is the third report of DONSON c.631C>T p.(Arg211Cys) in Turkish patients. While the recurrence in the same population suggests a founder effect, haplotype-based analysis is required. Thumb aplasia expands the known phenotype of DONSON-related MGORS, and the observed moderate course of growth retardation offers prognostic value. These findings highlight the importance of including DONSON in MGORS gene panels, considering population-specific variants, and systematically documenting rare phenotypic features to improve diagnosis, follow-up, and genetic counseling.