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Identification of a Novel Point Mutation in the LEMD3 Gene in an Infant With Buschke-Ollendorff Syndrome

Johanna Kratzsch, MD1; Diana Mitter, MD2; Mirjana Ziemer, MD1; Jürgen Kohlhase, MD3; Harald Voth, MD1
[+] Author Affiliations
1Department of Dermatology, Venerology, and Allergology, University of Leipzig, Leipzig, Germany
2Department of Human Genetics, University of Leipzig, Leipzig, Germany
3Department of Human Genetics, University of Freiburg, Freiburg, Germany
JAMA Dermatol. 2016;152(7):844-845. doi:10.1001/jamadermatol.2016.0350.
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This case report describes a novel point mutation in the LEMD3 gene in an infant with Buschke-Ollendorff syndrome.

Buschke-Ollendorff syndrome (BOS; OMIM 166700) is a rare autosomal dominant disease characterized by the variable occurrence of skin lesions (connective tissue nevi such as collagenomas or elastomas) and/or bone abnormalities known as osteopoikilosis. The underlying heterozygous loss-of-function mutation in the LEM domain-containing protein 3 gene (LEMD3) was identified in 2004.1 An integral protein of the inner nuclear membrane, LEMD3 antagonizes transforming growth factor β (TGF-β) and bone morphogenetic protein (BMP) signaling.1,2 Loss of LEMD3 expression leads to increased connective tissue and elastin production by fibroblasts via enhanced TGF-β and BMP signaling, thereby producing the characteristic clinical phenotype.3

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Figure 1.
Clinical and Pathologic Findings

A, Multiple yellowish papules coalescing into larger plaques on the left forearm. B, Accumulation of enlarged and fragmented elastic fibers in the mid-dermis under elastica van Gieson staining (original magnification ×200).

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Figure 2.
Genetic Sequence Analysis

Sequence analysis found a heterozygous novel loss-of-function mutation in exon 1 of the LEMD3 gene (c.1363c > t, p.q455*) that led to a nucleic acid exchange at position 1363 of the complementary DNA, which resulted in a premature stop codon at the translation level. Gln indicates glutamin; Leu, leucin.

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