Lihong Liao1, Hoong-Wei Gan2, Vivian Hwa1, Mehul Dattani2, Andrew Dauber1. 1. Cincinnati Center for Growth Disorders, Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA. 2. Section of Genetics and Epigenetics in Health and Disease, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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