Department of Human and Molecular Genetics, Clinical Genetics Services, VCU Health, Richmond, Virginia, USA.
Department of Pathology, VCU Health, Richmond, Virginia, USA.
Clin Genet. 2020 Jul;98(1):91-98. doi: 10.1111/cge.13765. Epub 2020 May 15.
Pathogenic variants in HNRNPH1 were first reported in 2018. The reported individual, a 13 year old boy with a c.616C>T (p.R206W) variant in the HNRNPH1 gene, was noted to have overlapping symptoms with those observed in HNRNPH2-related X-linked intellectual disability, Bain type (MRXSB), specifically intellectual disability and dysmorphic features. While HNRNPH1 variants were initially proposed to represent an autosomal cause of MRXSB, we report an additional seven cases which identify phenotypic differences from MRXSB. Patients with HNRNPH1 pathogenic variants diagnosed via WES were identified using clinical networks and GeneMatcher. Features unique to individuals with HNRNPH1 variants include distinctive dysmorphic facial features; an increased incidence of congenital anomalies including cranial and brain abnormalities, genitourinary malformations, and palate abnormalities; increased incidence of ophthalmologic abnormalities; and a decreased incidence of epilepsy and cardiac defects compared to those with MRXSB. This suggests that pathogenic variants in HNRNPH1 result in a related, but distinct syndromic cause of intellectual disability from MRXSB, which we refer to as HNRNPH1-related syndromic intellectual disability.
HNRNPH1 中的致病变异于 2018 年首次报道。报道的个体是一名 13 岁男孩，其 HNRNPH1 基因中存在 c.616C>T(p.R206W)变异，该个体表现出与 HNRNPH2 相关的 X 连锁智力残疾 Bain 型（MRXSB）重叠的症状，具体表现为智力残疾和发育异常。虽然 HNRNPH1 变异最初被提议代表 MRXSB 的常染色体病因，但我们报告了另外七个病例，这些病例确定了与 MRXSB 的表型差异。通过 WES 诊断为 HNRNPH1 致病性变异的患者是通过临床网络和 GeneMatcher 确定的。具有 HNRNPH1 变异个体的独特特征包括独特的发育异常面部特征；先天性异常的发生率增加，包括颅面和脑部异常、泌尿生殖系统畸形和腭裂异常；眼科异常的发生率增加；与 MRXSB 相比，癫痫和心脏缺陷的发生率降低。这表明 HNRNPH1 中的致病变异导致了与 MRXSB 相关的但不同的智力残疾综合征病因，我们将其称为 HNRNPH1 相关综合征性智力残疾。
