Ann Lab Med.  2017 Nov;37(6):540-543. 10.3343/alm.2017.37.6.540.

Novel 4-bp Intronic Deletion (c.1560+3_1560+6del) in LEMD3 in a Korean Patient With Osteopoikilosis

• Yoo IY
• Song JS
• Ki CS
• Kim JW
• Cha HS
• Min YK

• KMID: 2425998
• DOI: http://doi.org/10.3343/alm.2017.37.6.540

Abstract

Osteopoikilosis is an autosomal dominant bone disorder characterized by symmetric multiple osteosclerotic lesions throughout the axial and appendicular skeleton. Pathogenic variants in the LEMD3 have been identified as the cause of osteopoikilosis. LEMD3 encodes an inner nuclear membrane protein that interacts with bone morphogenetic protein (BMP) and transforming growth factor (TGF)-β pathways. We report the case of a 19-year-old man presenting with lower back pain and sciatica. His radiograph revealed bilateral and symmetrical multiple osteosclerotic bone lesions in both scapular areas. Sanger sequencing of LEMD3 revealed a four-base-pair deletion in intron 2 (c.1560+3_1560+6del), which was inherited from his father. We found that this four-base-pair deletion in intron 2 causes aberrant splicing and consequent deletion of exon 2. To the best of our knowledge, this is the first report of genetically confirmed osteopoikilosis in Korea.

Keyword

LEMD3; Osteopoikilosis; Sequencing; Deletion

MeSH Terms

Bone Morphogenetic Proteins
Exons
Fathers
Humans
Introns*
Korea
Low Back Pain
Nuclear Envelope
Osteopoikilosis*
Sciatica
Skeleton
Transforming Growth Factors
Young Adult
Bone Morphogenetic Proteins
Transforming Growth Factors

Figure

• 

  Fig. 1 Representative radiologic findings of the patients. (A) Ill-defined osteosclerotic lesions in both humoral head and scapula are observed in the proband. (B) Pelvis radiograph of the proband's father shows small, roundish radio-dense lesions in both proximal femurs and the iliac bone.Abbreviations: Lt, Left; Rt, Right.

• 

  Fig. 2 Novel splice site variant in the LEMD3 gene. (A) Sequencing pattern of LEMD3 shows overlapping peaks due to a heterozygous variant in intron 2 (c.1560+3_1560+6del; arrow). (B) Cloning of reverse transcription (RT)-PCR products reveals two clones: a normal clone and an abnormal clone without exon 2. (C) Schematic illustration of aberrant splicing due to the heterozygous 4-bp deletion.

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