Compound heterozygosity for two variants in BMP5 in human skeletal dysostosis with atrioventricular septal defect

Pernille Axél Gregersen; Anna Hammarsjö; Lise Graversen; Nis Brix; Hillevi Lindelöf; Uffe Birk Jensen; Stense Farholt; Sune Rubak; Jesper Bjerre; Serena G Piticchio; Thorkild Terkelsen; Gen Nishimura; Michel Bach Hellfritzsch; Giedre Grigelioniene

doi:10.1111/cge.14616

Compound heterozygosity for two variants in BMP5 in human skeletal dysostosis with atrioventricular septal defect

Pernille Axél Gregersen, Anna Hammarsjö, Lise Graversen, Nis Brix, Hillevi Lindelöf, Uffe Birk Jensen, Stense Farholt, Sune Rubak, Jesper Bjerre, Serena G Piticchio, Thorkild Terkelsen, Gen Nishimura, Michel Bach Hellfritzsch, Giedre Grigelioniene

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

The growth and development of the skeleton is regulated by bone morphogenetic proteins of which several are linked to genetic skeletal disorders. So far, no human skeletal malformations have been associated with variants in BMP5. Here, we report a patient with biallelic loss of function variants in BMP5 and a syndromic phenotype including skeletal dysostosis, dysmorphic features, hypermobility, laryngo-tracheo-bronchomalacia and atrioventricular septal defect. We discuss the phenotype in relation to the known tissue-specific expression of Bmp5 and similar morphological abnormalities previously reported in experimental animal models. Our findings suggest a new association between BMP5 variants and a range of developmental anomalies, involving ears, heart and skeleton, thereby increasing understanding of BMP5's role in human development.

Original language	English
Journal	Clinical Genetics
Volume	107
Issue	1
Pages (from-to)	78-82
Number of pages	5
ISSN	0009-9163
DOIs	https://doi.org/10.1111/cge.14616
Publication status	Published - Jan 2025

Keywords

BMP5
cardiac malformation
rare disease
skeletal dysostosis
skeletal dysplasia

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10.1111/cge.14616

Clinical Genetics - 2024 - Gregersen - Compound heterozygosity for two variants in BMP5 in human skeletal dysostosis withFinal published version, 983 KBLicence: CC BY-NC-ND

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Gregersen, P. A., Hammarsjö, A., Graversen, L., Brix, N., Lindelöf, H., Jensen, U. B., Farholt, S., Rubak, S., Bjerre, J., Piticchio, S. G., Terkelsen, T., Nishimura, G., Hellfritzsch, M. B., & Grigelioniene, G. (2025). Compound heterozygosity for two variants in BMP5 in human skeletal dysostosis with atrioventricular septal defect. Clinical Genetics, 107(1), 78-82. https://doi.org/10.1111/cge.14616

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title = "Compound heterozygosity for two variants in BMP5 in human skeletal dysostosis with atrioventricular septal defect",

abstract = "The growth and development of the skeleton is regulated by bone morphogenetic proteins of which several are linked to genetic skeletal disorders. So far, no human skeletal malformations have been associated with variants in BMP5. Here, we report a patient with biallelic loss of function variants in BMP5 and a syndromic phenotype including skeletal dysostosis, dysmorphic features, hypermobility, laryngo-tracheo-bronchomalacia and atrioventricular septal defect. We discuss the phenotype in relation to the known tissue-specific expression of Bmp5 and similar morphological abnormalities previously reported in experimental animal models. Our findings suggest a new association between BMP5 variants and a range of developmental anomalies, involving ears, heart and skeleton, thereby increasing understanding of BMP5's role in human development.",

keywords = "BMP5, cardiac malformation, rare disease, skeletal dysostosis, skeletal dysplasia",

author = "Gregersen, \{Pernille Ax{\'e}l\} and Anna Hammarsj{\"o} and Lise Graversen and Nis Brix and Hillevi Lindel{\"o}f and Jensen, \{Uffe Birk\} and Stense Farholt and Sune Rubak and Jesper Bjerre and Piticchio, \{Serena G\} and Thorkild Terkelsen and Gen Nishimura and Hellfritzsch, \{Michel Bach\} and Giedre Grigelioniene",

note = "{\textcopyright} 2024 The Author(s). Clinical Genetics published by John Wiley \& Sons Ltd.",

year = "2025",

month = jan,

doi = "10.1111/cge.14616",

language = "English",

volume = "107",

pages = "78--82",

journal = "Clinical Genetics",

issn = "0009-9163",

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Gregersen, PA, Hammarsjö, A, Graversen, L, Brix, N, Lindelöf, H, Jensen, UB, Farholt, S, Rubak, S, Bjerre, J, Piticchio, SG, Terkelsen, T, Nishimura, G, Hellfritzsch, MB & Grigelioniene, G 2025, 'Compound heterozygosity for two variants in BMP5 in human skeletal dysostosis with atrioventricular septal defect', Clinical Genetics, vol. 107, no. 1, pp. 78-82. https://doi.org/10.1111/cge.14616

Compound heterozygosity for two variants in BMP5 in human skeletal dysostosis with atrioventricular septal defect. / Gregersen, Pernille Axél; Hammarsjö, Anna; Graversen, Lise et al.
In: Clinical Genetics, Vol. 107, No. 1, 01.2025, p. 78-82.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Compound heterozygosity for two variants in BMP5 in human skeletal dysostosis with atrioventricular septal defect

AU - Gregersen, Pernille Axél

AU - Hammarsjö, Anna

AU - Graversen, Lise

AU - Brix, Nis

AU - Lindelöf, Hillevi

AU - Jensen, Uffe Birk

AU - Farholt, Stense

AU - Rubak, Sune

AU - Bjerre, Jesper

AU - Piticchio, Serena G

AU - Terkelsen, Thorkild

AU - Nishimura, Gen

AU - Hellfritzsch, Michel Bach

AU - Grigelioniene, Giedre

PY - 2025/1

Y1 - 2025/1

N2 - The growth and development of the skeleton is regulated by bone morphogenetic proteins of which several are linked to genetic skeletal disorders. So far, no human skeletal malformations have been associated with variants in BMP5. Here, we report a patient with biallelic loss of function variants in BMP5 and a syndromic phenotype including skeletal dysostosis, dysmorphic features, hypermobility, laryngo-tracheo-bronchomalacia and atrioventricular septal defect. We discuss the phenotype in relation to the known tissue-specific expression of Bmp5 and similar morphological abnormalities previously reported in experimental animal models. Our findings suggest a new association between BMP5 variants and a range of developmental anomalies, involving ears, heart and skeleton, thereby increasing understanding of BMP5's role in human development.

AB - The growth and development of the skeleton is regulated by bone morphogenetic proteins of which several are linked to genetic skeletal disorders. So far, no human skeletal malformations have been associated with variants in BMP5. Here, we report a patient with biallelic loss of function variants in BMP5 and a syndromic phenotype including skeletal dysostosis, dysmorphic features, hypermobility, laryngo-tracheo-bronchomalacia and atrioventricular septal defect. We discuss the phenotype in relation to the known tissue-specific expression of Bmp5 and similar morphological abnormalities previously reported in experimental animal models. Our findings suggest a new association between BMP5 variants and a range of developmental anomalies, involving ears, heart and skeleton, thereby increasing understanding of BMP5's role in human development.

KW - BMP5

KW - cardiac malformation

KW - rare disease

KW - skeletal dysostosis

KW - skeletal dysplasia

UR - https://www.scopus.com/pages/publications/85203151706

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DO - 10.1111/cge.14616

M3 - Journal article

C2 - 39239663

SN - 0009-9163

VL - 107

SP - 78

EP - 82

JO - Clinical Genetics

JF - Clinical Genetics

IS - 1

ER -

Compound heterozygosity for two variants in BMP5 in human skeletal dysostosis with atrioventricular septal defect

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