Tkemaladze Tinatin, Bregvadze Kakha, Abashishvili Luka, Chikvinidze Gocha, Delgado Vega Angelica Maria, Akbar Fizza, Khan Sara, Kirmani Salman
Department of Molecular and Medical Genetics, Tbilisi State Medical University, Tbilisi, Georgia.
Givi Zhvania Pediatric University Clinic, Tbilisi State Medical University, Tbilisi, Georgia.
Am J Med Genet A. 2025 Sep;197(9):e64116. doi: 10.1002/ajmg.a.64116. Epub 2025 May 12.
Pathogenic variants in IGHMBP2 have been associated with spinal muscular atrophy with respiratory distress type 1 (SMARD1) and Autosomal Recessive Charcot-Marie-Tooth disease type 2S (AR-CMT2S), as well as a relatively wide spectrum of rare, atypical phenotypes. We describe clinical and molecular features of five patients who have diverse clinical findings associated with known and novel IGHMBP2 pathogenic variants. Genotype-phenotype correlations are evident, highlighting the association of specific variants with SMARD1 or AR-CMT2S. This study expands the spectrum of the IGHMBP2-related disease and highlights the necessity to study diverse populations to enhance diagnostic accuracy and refine genotype-phenotype correlations.
IGHMBP2基因的致病性变异与1型呼吸窘迫型脊髓性肌萎缩症（SMARD1）和常染色体隐性遗传2S型夏科-马里-图斯病（AR-CMT2S）以及一系列相对广泛的罕见非典型表型有关。我们描述了五名患者的临床和分子特征，这些患者具有与已知和新型IGHMBP2致病性变异相关的不同临床发现。基因型与表型的相关性很明显，突出了特定变异与SMARD1或AR-CMT2S的关联。本研究扩展了IGHMBP2相关疾病的范围，并强调了研究不同人群以提高诊断准确性和完善基因型与表型相关性的必要性。
