Diagnostic Odyssey and Application of Targeted Exome Sequencing in the Investigation of Recurrent Infant Deaths in a Syrian Consanguineous Family: a Case of Spinal Muscular Atrophy with Respiratory Distress Type 1

• Published in: Journal of Korean medical science Vol. 34; no. 9; pp. e54 - 6
• Main Authors: Kim, Young A, Jin, Hye Young, Kim, Yoo-Mi
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Academy of Medical Sciences 11-03-2019; 대한의학회
• Subjects: Case Report; 의학일반; Infant Death; Exome Sequencing; Spinal Muscular Atrophy with Respiratory Distress Type 1
• ISSN: 1011-8934; 1598-6357
• DOI: 10.3346/jkms.2019.34.e54

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a rare autosomal recessive disorder caused by a defect in the immunoglobulin mu binding protein 2 (
) gene, leading to motor neuron degeneration. We identified an infant with SMARD1 by targeted exome sequencing from a consanguineous Syrian family having a history of recurrent infant deaths. The patient initially presented intrauterine growth retardation, poor sucking, failure to thrive, and respiratory failure at the age of two months, and an inborn error of metabolism was suspected at first. Over a period of one month, the infant showed rapid progression of distal muscular weakness with hand and foot contractures, which were suggestive of neuromuscular disease. Using targeted exome sequencing, the mutation in
was confirmed, although the first report was normal. Targeted exome sequencing enabled identification of the genetic cause of recurrent mysterious deaths in the consanguineous family. Additionally, it is suggested that a detailed phenotypic description and communication between bioinformaticians and clinicians is important to reduce false negative results in exome sequencing.