■GJC2中的纯合和复合杂合变体,编码连接蛋白-47蛋白的基因,导致Pelizaeus-Merzbacher-like疾病1型或2型白细胞营养不良(HLD2),严重的婴儿发作性脑白质营养不良,很少有一些较温和的表型,例如遗传性痉挛性截瘫(HSP)44型(SPG44)和亚临床脑白质营养不良。在这里,我们报道了一个具有家族内表型异质性的伊朗GJC2相关家族,并对文献进行了综述。
■对伊朗先证者进行了全外显子组测序,最初被诊断为HSP病例。分析数据并通过PCR和Sanger测序确认候选变体,随后在家族成员中检查以进行共分离分析。对该家庭所有受影响的个体进行了仔细的临床和临床评估,并与以前报道的GJC2相关家庭进行了比较。
■一种新的纯合变体,c.G14T:p.Ser5Ile,在GJC2基因中被鉴定。该变体与家庭成员中的疾病状态共分离。所有患者的临床评估显示该家族中两种不同的GJC2相关表型;先证者表现为复杂形式的HSP,而他的两个受影响的姐妹都呈现HLD2表型。
■到目前为止,HSP和GJC2变异体之间的相关性已有报道。这里,确定了第二例SPG44,强调GJC2是引起HSP的基因。所以,建议在具有HSP或HSP样表型的患者中,尤其是在他们的脑MRI中进行GJC2筛查.此外,第一次,报告了“两种不同的GJC2相关表型:HLD2和HSP”的家族内表型异质性。GJC2的这种家族内表型异质性可以强调这些疾病的共同病理生理学。
UNASSIGNED: Homozygous and compound heterozygous variants in GJC2, the gene encoding connexin-47 protein, cause Pelizaeus-Merzbacher-like disease type 1 or hypomyelinating leukodystrophy 2 (HLD2), a severe infantile-onset hypomyelinating leukodystrophy, and rarely some milder phenotypes like hereditary spastic paraplegia (HSP) type 44 (SPG44) and subclinical leukodystrophy. Herein, we report an Iranian GJC2-related family with intrafamilial phenotypic heterogeneity and
review the literatures.
UNASSIGNED: Whole-exome sequencing was performed for an Iranian proband, who was initially diagnosed as HSP case. Data were analyzed and the candidate variant was confirmed by PCR and Sanger sequencing subsequently checked in family members to co-segregation analysis. A careful clinical and paraclinical evaluation of all affected individuals of the family was done and compared with previous reported GJC2-related families.
UNASSIGNED: A novel homozygous variant, c.G14T:p.Ser5Ile, in the GJC2 gene was identified. The variant was co-segregated with the disease status in the family members. Clinical evaluation of all patients showed two distinct GJC2-related phenotypes in this family; the proband presented a complicated form of HSP, whereas both his affected sisters presented a HLD2 phenotype.
UNASSIGNED: Up to now, correlation between HSP and GJC2 variants has been reported once. Here, the second case of SPG44 was identified that emphasizes on GJC2 as a HSP-causing gene. So, the screening of GJC2 in patients with HSP or HSP-like phenotypes especially with hypomyelination in their brain MRI is recommended. Also, for the first time, intrafamilial phenotypic heterogeneity for \"two distinct GJC2-related phenotypes: HLD2 and HSP\" was reported. Such intrafamilial phenotypic heterogeneity for GJC2 can emphasize on the shared pathophysiology of these disorders.