Lam Zena, Albaba Shadi, Study Ddd, Balasubramanian Meena
Yorkshire Regional Genetics Service, Leeds Teaching Hospitals NHS Trust, Leeds.
Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Foundation Trust, Sheffield.
Clin Dysmorphol. 2020 Jan;29(1):10-16. doi: 10.1097/MCD.0000000000000298.
With the increasing availability and clinical use of exome and whole-genome sequencing, reverse phenotyping is now becoming common practice in clinical genetics. Here, we report a patient identified through the Wellcome Trust Deciphering Developmental Disorders study who has homozygous pathogenic variants in CC2D2A and a de-novo heterozygous pathogenic variant in KIDINS220. He presents with developmental delay, intellectual disability, and oculomotor apraxia. Reverse phenotyping has demonstrated that he likely has a composite phenotype with contributions from both variants. The patient is much more mildly affected than those with Joubert Syndrome or Spastic paraplegia, intellectual disability, nystagmus, and obesity, the conditions associated with CC2D2A and KIDINS220 respectively, and therefore, contributes to the phenotypic variability associated with the two conditions.
随着外显子组和全基因组测序技术的日益普及及其在临床上的应用，反向表型分析如今在临床遗传学中已成为常见做法。在此，我们报告一名通过威康信托基金会发育障碍解析研究鉴定出的患者，该患者在CC2D2A基因中有纯合致病性变异，在KIDINS220基因中有一个新发杂合致病性变异。他表现出发育迟缓、智力残疾和眼球运动失用症。反向表型分析表明，他可能具有一种由两种变异共同导致的复合表型。该患者的症状比分别与CC2D2A和KIDINS220相关的Joubert综合征或痉挛性截瘫、智力残疾、眼球震颤和肥胖患者要轻得多，因此，这也导致了与这两种疾病相关的表型变异性。
