Clinical diagnostic exome evaluation for an infant with a lethal disorder: genetic diagnosis of TARP syndrome and expansion of the phenotype in a patient with a newly reported RBM10 alteration

Diagnostic Exome Sequencing (DES) has been shown to be an effective tool for diagnosis individuals with suspected genetic conditions. We report a male infant born with multiple anomalies including bilateral dysplastic kidneys, cleft palate, bilateral talipes, and bilateral absence of thumbs and firs...

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Published in:	BMC medical genetics 2017-06, Vol.18 (1), p.60-60, Article 60
Main Authors:	Powis, Zöe, Hart, Alexa, Cherny, Sara, Petrik, Igor, Palmaer, Erika, Tang, Sha, Jones, Carolyn
Format:	Article
Language:	eng
Subjects:	Analysis Anus Aplasia Automation Bioinformatics Birth defects Case Report Cleft lip/palate Clinical diagnostic sequencing Clubfoot Clubfoot - diagnosis Clubfoot - genetics Congenital defects Congenital diseases Defects Diagnosis Diagnostic equipment (Medical) Disease Exome Exome sequencing Family medical history Fatal Outcome Genes Genetic counseling Genetic disorders Genetic screening Genomes Genomics Genotype & phenotype Heart Defects, Congenital - diagnosis Heart Defects, Congenital - genetics Hereditary diseases Human Humans Infant Male Medical prognosis Mutation Neonates Oligodactyly Patients Phenotype Pierre Robin Syndrome - diagnosis Pierre Robin Syndrome - genetics Prognosis Proteins RBM10 protein Ribonucleic acid RNA RNA-Binding Proteins - genetics Sequence Analysis, DNA TARP syndrome Ultrasonic imaging
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Summary:	Diagnostic Exome Sequencing (DES) has been shown to be an effective tool for diagnosis individuals with suspected genetic conditions. We report a male infant born with multiple anomalies including bilateral dysplastic kidneys, cleft palate, bilateral talipes, and bilateral absence of thumbs and first toes. Prenatal testing including chromosome analysis and microarray did not identify a cause for the multiple congenital anomalies. Postnatal diagnostic exome studies (DES) were utilized to find a molecular diagnosis for the patient. Exome sequencing of the proband, mother, and father showed a previously unreported maternally inherited RNA binding motif protein 10 (RBM10) c.1352_1353delAG (p.E451Vfs*66) alteration. Mutations in RBM10 are associated with TARP syndrome, an X-linked recessive disorder originally described with cardinal features of talipes equinovarus, atrial septal defect, Robin sequence, and persistent left superior vena cava. DES established a molecular genetic diagnosis of TARP syndrome for a neonatal patient with a poor prognosis in whom traditional testing methods were uninformative and allowed for efficient diagnosis and future reproductive options for the parents. Other reported cases of TARP syndrome demonstrate significant variability in clinical phenotype. The reported features in this infant including multiple hemivertebrae, imperforate anus, aplasia of thumbs and first toes have not been reported in previous patients, thus expanding the clinical phenotype for this rare disorder.
ISSN:	1471-2350 1471-2350