背景:特发性基底节钙化,也被称为Fahr病,它是一种神经系统疾病,其特征是由杂合SLC20A2突变引起的颅内钙化。钙化患者可以无症状或表现出广泛的神经精神症状,包括帕金森病,震颤,肌张力障碍,共济失调,和癫痫发作。
目的:本研究的目的是研究SLCA20A2基因的临床意义,并通过一个家族鉴定新的表型。
方法:两个生长迟缓的兄弟姐妹,双侧白内障,小头畸形,和惊厥被纳入研究。MRI显示脑萎缩,call体发育不全,微钙化。进行染色体微阵列分析以鉴定拷贝数变异的存在。进行了单个IV-I的整个外显子组测序分析,进行Sanger测序进行分离。
结果:全外显子组测序显示SLC20A2基因的纯合NM_006749.5:c.1794+1G>A。Sanger测序证实受影响的兄弟姐妹是纯合的,父母是杂合的。
结论:SLC20A2基因杂合突变与成人发病表型相关,而纯合SLC20A2突变在两个受影响的兄弟姐妹,我们在我们的研究报告导致严重的临床包括生长迟缓,双侧白内障,小头畸形,和抽搐。我们表明,导致Fahr病的SLC20A2基因的双等位基因突变会导致与已知情况相反的更严重的表型。这两个兄弟姐妹,表现出相似的音型和基因型特征,将是文献中发表的儿科年龄组中最年轻的病例。
BACKGROUND: Idiopathic basal ganglia calcification, also known as Fahr\'s disease, it is a neurological disease characterized by intracranial calcification caused by heterozygous SLC20A2 mutations. Patients with calcifications can either be asymptomatic or show a wide spectrum of neuropsychiatric symptoms, including parkinsonism, tremor, dystonia, ataxia, and seizures.
OBJECTIVE: The aim of this study was to investigating the clinical implications of the SLCA20A2 gene and identifying a new phenotype through a family.
METHODS: Two siblings with growth retardation, bilateral cataracts, microcephaly, and convulsion were included in the study. The MRI showed cerebral atrophy, corpus callosum hypoplasia, microcalcifications. Chromosomal microarray analysis was performed to identify the existence of copy number variation. The whole exome sequencing analysis of the individual IV-I was performed, and Sanger sequencing was performed for segregation.
RESULTS: Whole exome sequencing revealed a homozygous NM_006749.5:c.1794 + 1G > A of the SLC20A2 gene. The Sanger sequencing confirmed the affected siblings were homozygous and the parents were heterozygous.
CONCLUSIONS: SLC20A2 gene heterozygous mutations were associated with the adult-onset phenotype, while homozygous SLC20A2 mutations in the two affected siblings we reported in our study resulted in a severe clinic including growth retardation, bilateral cataracts, microcephaly, and convulsion. We showed that biallelic mutations in the SLC20A2 gene that cause the Fahr\'s disease lead to more severe phenotypes contrary to what is known. The two siblings, showing similar phonotypic and genotypic characteristics, would be the youngest cases in the pediatric age group published in the literature.