Cincinnati Center for Growth Disorders, Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Section of Genetics and Epigenetics in Health and Disease, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.
Horm Res Paediatr. 2017;88(5):364-370. doi: 10.1159/000477907. Epub 2017 Jul 4.
Short stature can be caused by mutations in a multitude of different genes. 3-M syndrome is a rare growth disorder marked by severe pre- and postnatal growth retardation along with subtle dysmorphic features. There have only been 2 prior reports of mutations in CCDC8 causing 3-M syndrome.
Two patients presenting with mild short stature underwent whole exome sequencing. The mutation was confirmed via Sanger sequencing. We compare the clinical characteristics of our 2 patients to patients previously reported with mutations in the same gene.
Exome sequencing identified a homozygous frameshift mutation in CCDC8 in both patients. They presented with a much milder phenotype than previously described patients with the same mutation.
In this study, we report a case of 2 sisters with relatively mild short stature who were found via exome sequencing to carry a previously reported homozygous mutation in CCDC8. These patients expand the anthropometric phenotype of 3-M syndrome and demonstrate the power of exome sequencing in the diagnosis of children with short stature. 3-M syndrome should be considered in children with mild skeletal abnormalities, normal/high growth hormone-IGF axis parameters, and normal intelligence.
身材矮小可能由多种不同基因的突变引起。3-M 综合征是一种罕见的生长障碍，其特征为严重的产前和产后生长迟缓，以及微妙的畸形特征。仅有 2 份先前关于 CCDC8 基因突变导致 3-M 综合征的报告。
两名表现为轻度身材矮小的患者接受了全外显子组测序。通过 Sanger 测序确认了突变。我们将我们的 2 名患者的临床特征与具有相同基因突变的先前报道的患者进行了比较。
外显子组测序在两名患者中均发现了 CCDC8 的纯合移码突变。他们的表型比先前报道的具有相同突变的患者要轻得多。
在这项研究中，我们报告了 2 例具有相对轻度身材矮小的姐妹的病例，通过外显子组测序发现她们携带先前报道的 CCDC8 纯合突变。这些患者扩展了 3-M 综合征的人体测量表型，并展示了外显子组测序在诊断身材矮小儿童中的强大功能。3-M 综合征应在骨骼异常轻微、生长激素-IGF 轴参数正常/高和智力正常的儿童中考虑。
