Department of Medical Genetics, Osaka Women's and Children's Hospital, 840 Murodo-cho, Izumi, Osaka, 594-1101, Japan.
Department of Medical Science Mathematics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Neurol Sci. 2021 Jul;42(7):2975-2978. doi: 10.1007/s10072-021-05152-y. Epub 2021 Mar 11.
Mutations of theADCY5 have been identified in patients with familial dyskinesia, early-onsetautosomal dominant chorea and dystonia, and benign hereditary chorea. Most ofthe ADCY5 mutations are de novo or transmitted in an autosomal dominantfashion. Only two pedigrees are known to show autosomal recessive inheritance.
We report twosiblings with severe ID, dystonic movement, and growth failure with unknownetiology.
We planned a proband-parentapproach using whole exome sequencing.
Homozygous mutationin exon 21 of the ADCY5 (p.R1238W) was identified in the siblings. Althoughtheir parents were heterozygous for the mutation, they were free from clinicalmanifestations.
Our results furtherexpand the phenotype/genotype correlations of the ADCY5-related disorders.Mutations of ADCY5 should be considered in pediatric patients with ID andinvoluntary movement.
ADCY5 的突变已在家族性运动障碍、早发性常染色体显性舞蹈症和肌张力障碍以及良性遗传性舞蹈症患者中被发现。大多数 ADCY5 突变是从头发生或呈常染色体显性遗传方式传递的。仅有两个家系表现为常染色体隐性遗传。
我们报告了两例具有严重智力障碍、肌张力障碍运动和不明病因生长障碍的同胞。
我们计划采用全外显子组测序进行先证者-父母的研究方法。
在这对同胞中发现 ADCY5 外显子 21 中的纯合突变（p.R1238W）。尽管他们的父母为该突变的杂合子，但他们没有临床表现。
我们的结果进一步扩展了 ADCY5 相关疾病的表型/基因型相关性。在具有智力障碍和不自主运动的儿科患者中，应考虑 ADCY5 的突变。
