Medical Genetics Sector, Faculty of Medicine, Federal University of Alagoas, Maceió, Alagoas, Brazil.
Clinical Genetics Service, Medical Genetics Sector, Faculty of Medicine, University Hospital, Federal University of Alagoas, Maceió, Alagoas, Brazil.
Neurol Sci. 2024 Jun;45(6):2705-2710. doi: 10.1007/s10072-023-07271-0. Epub 2023 Dec 30.
The Brazilian Northeast region is notable for its high prevalence of consanguineous marriages and isolated populations, which has led to a significant prevalence of rare genetic disorders. This study describes the clinical presentation of four affected individuals from the same family, comprising two siblings and their cousins, with ages ranging from 11 to 20 years.
In a small and isolated community in Northeastern Brazil, affected individuals initially underwent a clinical assessment. Subsequently, written consent was obtained from their legal guardians, and an extensive clinical evaluation was conducted at a medical genetics center. Family data provided the basis for constructing the pedigree, and biological samples (blood or oral swabs) were collected from both affected and unaffected family members. Following informed consent from one patient, Whole Exome Sequencing (WES) was carried out, encompassing exome sequencing, assembly, genotyping, and annotation. A potentially deleterious variant was then singled out for further segregation analysis through Sanger Sequencing, involving both the proband and select family members.
These individuals exhibit severe neurodevelopmental delays, encompassing symptoms such as spastic paraplegia, neuropathy, intellectual impairments, and language challenges. Through next-generation sequencing (NGS) techniques, a previously unreported homozygous variant within the ERLIN2 gene linked to spastic paraplegia 18 (SPG18) was identified across all four patients. Also, all patients displayed childhood cataract, expanding the known clinical spectrum of SPG18.
巴西东北部地区以高发的近亲婚姻和孤立人群为特点，这导致了罕见遗传疾病的高发。本研究描述了来自同一家庭的 4 名受影响个体的临床表现，包括 2 名兄弟姐妹及其表亲，年龄在 11 至 20 岁之间。
在巴西东北部的一个小而孤立的社区，受影响的个体首先接受了临床评估。随后，从他们的法定监护人处获得书面同意，并在医学遗传学中心进行了广泛的临床评估。家庭数据为构建家系提供了基础，并从受影响和未受影响的家庭成员中收集了生物样本（血液或口腔拭子）。在一名患者同意后，进行了全外显子组测序（WES），包括外显子组测序、组装、基因分型和注释。然后通过 Sanger 测序对潜在的有害变异进行进一步的分离分析，涉及先证者和部分家庭成员。
这些个体表现出严重的神经发育迟缓，包括痉挛性截瘫、神经病、智力障碍和语言障碍等症状。通过下一代测序（NGS）技术，在所有 4 名患者中均发现了一个以前未报道的 ERLIN2 基因内与痉挛性截瘫 18 型（SPG18）相关的纯合变异。此外，所有患者均表现出儿童期白内障，扩大了 SPG18 的已知临床谱。
