J Korean Med Sci.  2019 Mar;34(9):e54. 10.3346/jkms.2019.34.e54.

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

• Kim YA
• Jin HY
• Kim YM

• KMID: 2441911
• DOI: http://doi.org/10.3346/jkms.2019.34.e54

Abstract

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 (IGHMBP2) 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 IGHMBP2 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.

Keyword

Exome Sequencing; Infant Death; Spinal Muscular Atrophy with Respiratory Distress Type 1

MeSH Terms

Carrier Proteins
Contracture
Exome*
Failure to Thrive
Fetal Growth Retardation
Foot
Hand
Humans
Immunoglobulins
Infant Death*
Infant*
Metabolism
Motor Neurons
Muscle Weakness
Muscular Atrophy, Spinal*
Neuromuscular Diseases
Respiratory Insufficiency
Carrier Proteins
Immunoglobulins