التفاصيل البيبلوغرافية
| العنوان: |
The Genetic Landscape of Children Born Small for Gestational Age with Persistent Short Stature. |
| المؤلفون: |
Toni, Ledjona, Plachy, Lukas, Dusatkova, Petra, Amaratunga, Shenali Anne, Elblova, Lenka, Sumnik, Zdenek, Kolouskova, Stanislava, Snajderova, Marta, Obermannova, Barbora, Pruhova, Stepanka, Lebl, Jan |
| المصدر: |
Hormone Research in Paediatrics; 2024, Vol. 97 Issue 1, p40-52, 13p |
| مصطلحات موضوعية: |
SMALL for gestational age, SHORT stature, PITUITARY dwarfism, BIRTH weight, GROWTH plate, GESTATIONAL age |
| مستخلص: |
Introduction: Among children born small for gestational age, 10–15% fail to catch up and remain short (SGA-SS). The underlying mechanisms are mostly unknown. We aimed to decipher genetic aetiologies of SGA-SS within a large single-centre cohort. Methods: Out of 820 patients treated with growth hormone (GH), 256 were classified as SGA-SS (birth length and/or birth weight <−2 SD for gestational age and life-minimum height <−2.5 SD). Those with the DNA triplet available (child and both parents) were included in the study (176/256). Targeted testing (karyotype/FISH/MLPA/specific Sanger sequencing) was performed if a specific genetic disorder was clinically suggestive. All remaining patients underwent MS-MLPA to identify Silver-Russell syndrome, and those with unknown genetic aetiology were subsequently examined using whole-exome sequencing or targeted panel of 398 growth-related genes. Genetic variants were classified using ACMG guidelines. Results: The genetic aetiology was elucidated in 74/176 (42%) children. Of these, 12/74 (16%) had pathogenic or likely pathogenic (P/LP) gene variants affecting pituitary development (LHX4, OTX2, PROKR2, PTCH1, POU1F1), the GH-IGF-1 or IGF-2 axis (GHSR, IGFALS, IGF1R, STAT3, HMGA2), 2/74 (3%) the thyroid axis (TRHR, THRA), 17/74 (23%) the cartilaginous matrix (ACAN, various collagens, FLNB, MATN3), and 7/74 (9%) the paracrine chondrocyte regulation (FGFR3, FGFR2, NPR2). In 12/74 (16%), we revealed P/LP affecting fundamental intracellular/intranuclear processes (CDC42, KMT2D, LMNA, NSD1, PTPN11, SRCAP, SON, SOS1, SOX9, TLK2). SHOX deficiency was found in 7/74 (9%), Silver-Russell syndrome in 12/74 (16%) (11p15, UPD7), and miscellaneous chromosomal aberrations in 5/74 (7%) children. Conclusions: The high diagnostic yield sheds a new light on the genetic landscape of SGA-SS, with a central role for the growth plate with substantial contributions from the GH-IGF-1 and thyroid axes and intracellular regulation and signalling. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
