Yalcintepe Sinem, Maras Tuba, Kizilyar Ilke, Sezginer Guler Hazal, Zhuri Drenushe, Atli Engin, Ozen Yasemin, Gurkan Hakan
Department of Medical Genetics, Faculty of Medicine, Trakya University, Edirne, Turkey.
Mol Syndromol. 2024 Aug;15(4):284-288. doi: 10.1159/000536386. Epub 2024 Feb 16.
Canavan disease is an autosomal recessive disorder that causes accumulation of N-acetyl ASPArtic acid in the brain due to ASPArtoacylase deficiency with homozygous or compound heterozygous pathogenic variants in the gene located on the short arm of chromosome 17. Clinical findings are hypotonia, progressive macrocephaly, deafness, nystagmus, blindness, and brain atrophy.
A one-year-old female case was evaluated in our medical genetics clinic for hypotonia, nystagmus, and strabismus. Chromosome analysis and array-comparative genomic hybridization showed no pathology. Clinical exome sequencing by next-generation sequencing was performed and a homozygous likely pathogenic variant NM_000049.4():c.857C > A p.(Ala286Asp) was identified. Sanger sequencing of the parents showed that the index case had a homozygous genotype, the father was heterozygous and the mother had a wild genotype for the identified variant in . A single nucleotide polymorphism (SNP) array test was planned for the family to explain this homozygosity and a loss of maternal heterozygosity was determined in the 17p13.3-p13.2 region of the gene.
In this report, we aimed to present the first case of Canavan disease with maternal loss of heterozygosity in the gene.
卡纳万病是一种常染色体隐性疾病，由于位于17号染色体短臂上的基因存在纯合或复合杂合致病性变异，导致天冬氨酸酰基转移酶缺乏，进而引起大脑中N - 乙酰天冬氨酸蓄积。临床症状包括肌张力减退、进行性巨头畸形、耳聋、眼球震颤、失明和脑萎缩。
一名1岁女性因肌张力减退、眼球震颤和斜视在我们的医学遗传学门诊接受评估。染色体分析和阵列比较基因组杂交未发现病变。通过下一代测序进行临床外显子组测序，发现一个纯合的可能致病性变异NM_000049.4():c.857C > A p.(Ala286Asp)。对父母进行的桑格测序显示，索引病例具有纯合基因型，父亲为杂合子，母亲对于所鉴定的基因变异具有野生基因型。计划对该家庭进行单核苷酸多态性（SNP）阵列检测以解释这种纯合性，并在该基因的17p13.3 - p13.2区域确定了母源杂合性缺失。
在本报告中，我们旨在呈现首例该基因存在母源杂合性缺失的卡纳万病病例。
