Skrypnyk Cristina, Husain Aseel Ahmed, Hassan Hisham Y, Ahmed Jameel, Darwish Abdulla, Almusalam Latifa, Ben Khalaf Noureddine, Al Qashar Fahad
Department of Molecular Medicine, Al-Jawhara Centre for Molecular Medicine, Arabian Gulf University, Manama, Bahrain.
Department of Medical Genetics, University Medical Center, King Abdulla Medical City, Manama, Bahrain.
Front Genet. 2023 Mar 21;14:1098102. doi: 10.3389/fgene.2023.1098102. eCollection 2023.
Nemaline myopathies are a heterogeneous group of congenital myopathies caused by mutations in different genes associated with the structural and functional proteins of thin muscular filaments. Most patients have congenital onset characterized by hypotonia, respiratory issues, and abnormal deep tendon reflexes, which is a phenotype encountered in a wide spectrum of neuromuscular disorders. Whole-exome sequencing (WES) contributes to a faster diagnosis and facilitates genetic counseling. Here, we report on two Arab patients from consanguineous families diagnosed with nemaline myopathy of different phenotype spectrum severities. Clinical assessment and particular prenatal history raised suspicion of neuromuscular disease. WES identified homozygous variants in and . Muscle biopsy and muscle magnetic resonance imaging studies linked the genetic testing results to the clinical phenotype. The novel variant in the gene resulted in a classical type 2 nemaline myopathy, while the gene variant led to a severe phenotype of nemaline myopathy, type 8. Both patients were identified as having other gene variants with uncertain roles in their complex phenotypes. This study enriches the phenotypic spectrum of nemaline myopathy caused by and variants and highlights the importance of detailed prenatal, neonatal, and infancy assessments of muscular weakness associated with complex systemic features. Variants of uncertain significance in genes associated with nemaline myopathy may be correlated with the phenotype. Early, multidisciplinary intervention can improve the outcome in patients with mild forms of nemaline myopathies. WES is essential for clarifying complex clinical phenotypes encountered in patients from consanguineous families. Targeted carrier screening of extended family members would enable accurate genetic counseling and potential genetic prevention.
杆状体肌病是一组由与细肌丝结构和功能蛋白相关的不同基因突变引起的先天性肌病。大多数患者先天性起病，表现为肌张力低下、呼吸问题和异常的深部腱反射，这是广泛的神经肌肉疾病中常见的一种表型。全外显子组测序（WES）有助于更快地做出诊断并促进遗传咨询。在此，我们报告了两名来自近亲家庭的阿拉伯患者，他们被诊断患有不同表型谱严重程度的杆状体肌病。临床评估和详细的产前病史引发了对神经肌肉疾病的怀疑。WES在[具体基因1]和[具体基因2]中鉴定出纯合变异。肌肉活检和肌肉磁共振成像研究将基因检测结果与临床表型联系起来。[具体基因1]中的新变异导致了经典的2型杆状体肌病，而[具体基因2]的变异导致了严重的8型杆状体肌病表型。两名患者还被鉴定出具有其他在其复杂表型中作用不确定的基因变异。本研究丰富了由[具体基因1]和[具体基因2]变异引起的杆状体肌病的表型谱，并强调了对与复杂全身特征相关的肌肉无力进行详细产前、新生儿和婴儿期评估的重要性。与杆状体肌病相关基因中意义不确定的变异可能与表型相关。早期多学科干预可改善轻度杆状体肌病患者的预后。WES对于阐明近亲家庭患者中遇到的复杂临床表型至关重要。对大家庭成员进行有针对性的携带者筛查将有助于进行准确的遗传咨询和潜在的遗传预防。
