Department of Molecular Medicine and Medical Biotechnology, University Federico II, 80131 Naples, Italy.
Endocrinology and Auxology Unit, Pediatrics Speciality Department, A.O.R.N. Santobono-Pausilipon, 80131 Naples, Italy.
Int J Mol Sci. 2024 Oct 10;25(20):10913. doi: 10.3390/ijms252010913.
Defects of the gene have been mainly associated with pseudohypoparathyroidism Ia. To date, pathogenic missense, frameshift, non-sense and splicing variants have been described in all the 13 exons of the gene. Of them, a specific mutation, namely the 4 bp deletion c.565_568delGACT, is currently considered a mutation hotspot. Recent articles performed genotype-phenotype correlations in patients with -related pseudohypoparathyroidism Ia (PHP1a) but a specific focus on this hotspot is still lacking. We reported two cases, from our department, of PHP1a associated with c.565_568delGACT deletion and performed a literature review of all the previously reported cases of the 4 bp deletion hotspot. We found a higher prevalence of brachydactyly, round face, intellectual disability and subcutaneous/heterotopic ossifications in patients with the c.565_568delGACT as compared to the other variants in the gene. The present study highlights the different prevalence of some clinical features in patients with the c.565_568delGACT variant in the gene, suggesting the possibility of a personalized diagnostic follow-up and surveillance for these patients.
该基因的缺陷主要与假性甲状旁腺功能减退症 Ia 有关。迄今为止，已经在该基因的所有 13 个外显子中描述了致病性错义、移码、无义和剪接变异。其中，一个特定的突变，即 c.565_568delGACT 4bp 缺失，目前被认为是一个突变热点。最近的文章对假性甲状旁腺功能减退症 Ia（PHP1a）相关的基因患者进行了基因型-表型相关性研究，但对该热点的具体关注仍然缺乏。我们报告了两个与 c.565_568delGACT 缺失相关的 PHP1a 病例，并对所有先前报道的 4bp 缺失热点病例进行了文献复习。我们发现，与该基因中的其他变体相比，携带 c.565_568delGACT 的患者更易出现短指畸形、圆脸、智力障碍和皮下/异位骨化。本研究强调了基因中 c.565_568delGACT 变异患者一些临床特征的不同流行率，提示对这些患者进行个性化诊断随访和监测的可能性。
