Clinical-genetic Profile in Patients of Roma Origin with Spinal Muscular Atrophy with Bone Fractures Type 2

Abstract

Spinal muscular atrophy with congenital bone fractures-2 (SMABF2) is a severe autosomal recessive neuromuscular condition, characterized by prenatal-onset spinal muscular atrophy, multiple congenital contractures consistent with arthrogryposis multiplex congenita, respiratory distress, and congenital bone fractures caused by mutations in the ASCC1 gene. We present two unrelated newborns with congenital muscular weakness, joint contractures and long bone fractures, deceased at early infant age. Next-generation sequencing technology validated by Sanger sequencing aided the post mortem identification of the novel ASCC1: c.626+1G>A mutation in homozygous state, and respectively the final genetic diagnosis of SMABF2, in a deceased male Roma newborn (Patient 1) with severe muscular hypotonia, multiple congenital contractures and long bone fractures. Subsequently, based on this result we succeeded to establish the clinical-genetic diagnosis of SMABF in a female Roma newborn (Patient 2) with similar phenotype by detection of the same disease causing mutation ASCC1: c.626+1G>A in a homozygous state. Similar to other unique rare autosomal recessive disorders discovered in Bulgarian Roma population we may presume a higher carrier frequency of the mutation in c. c.626+1G>A in ASCC1 gene in Bulgarian Roma population due to a possible founder effect. Implementation of population based genetic screening is a feasible option to discuss.

Key words: spinal muscular atrophy, bone fractures, arthrogryposis multiplex congenita, Roma mutations

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Address for correspondence

National Genetic Laboratory, SBALAG “Machin dom”

2, “Zdrave”, Str.

1431, Sofia

Bulgaria

e-mail: bradinova@maichindom.com