Identification of novel ACAN mutations in two Chinese families and genotype–phenotype correlation in patients with 74 pathogenic ACAN variations

Abstract Background ACAN (OMIM 155760) is located on chromosome 15q26 and encodes the production of aggrecan. Aggrecan is a large chondroitin sulfate proteoglycan with a molecular weight of 254 kDa and contains 2530 amino acids. It is a critical structural component of the extracellular matrix of ca...

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Autores principales:	Ming Wei, Yanqin Ying, Zhuxi Li, Ying Weng, Xiaoping Luo
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/c83e253187934bb6bac6f6dd419ebd92
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spelling	oai:doaj.org-article:c83e253187934bb6bac6f6dd419ebd922021-11-21T19:38:53ZIdentification of novel ACAN mutations in two Chinese families and genotype–phenotype correlation in patients with 74 pathogenic ACAN variations2324-926910.1002/mgg3.1823https://doaj.org/article/c83e253187934bb6bac6f6dd419ebd922021-11-01T00:00:00Zhttps://doi.org/10.1002/mgg3.1823https://doaj.org/toc/2324-9269Abstract Background ACAN (OMIM 155760) is located on chromosome 15q26 and encodes the production of aggrecan. Aggrecan is a large chondroitin sulfate proteoglycan with a molecular weight of 254 kDa and contains 2530 amino acids. It is a critical structural component of the extracellular matrix of cartilage, including growth plate, articular, and intervertebral disk cartilage. It plays a key role in bone development. Methods Here, we describe two pedigrees with loss‐of‐function variants in ACAN. Whole exome sequencing was performed for the probands from each family. We illustrate the clinical variability associated with ACAN variants. Results The proband of pedigree A manifested short stature, relative macrocephaly, mild flat nasal bridge, low‐set ears, short neck, and short thumbs. The proband of pedigree B had short height, abnormal vertebral development, and central precocious puberty. By trio‐based whole exome sequencing and in silico analyses, we identified two de novo heterozygous variants of ACAN: NM_013227.4: c.116dupT, p.Arg40Glufs51 and NM_013227.4: c.2367delC, p.Ser790Glnfs20 (accession number: AC103982.10). Conclusion The clinical manifestations of ACAN gene variants are diverse. ACAN gene variants are important genetic factors for short stature and should be considered as the differential diagnosis of children with idiopathic short stature (ISS).Ming WeiYanqin YingZhuxi LiYing WengXiaoping LuoWileyarticleGeneticsQH426-470ENMolecular Genetics & Genomic Medicine, Vol 9, Iss 11, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Ming Wei Yanqin Ying Zhuxi Li Ying Weng Xiaoping Luo Identification of novel ACAN mutations in two Chinese families and genotype–phenotype correlation in patients with 74 pathogenic ACAN variations
description	Abstract Background ACAN (OMIM 155760) is located on chromosome 15q26 and encodes the production of aggrecan. Aggrecan is a large chondroitin sulfate proteoglycan with a molecular weight of 254 kDa and contains 2530 amino acids. It is a critical structural component of the extracellular matrix of cartilage, including growth plate, articular, and intervertebral disk cartilage. It plays a key role in bone development. Methods Here, we describe two pedigrees with loss‐of‐function variants in ACAN. Whole exome sequencing was performed for the probands from each family. We illustrate the clinical variability associated with ACAN variants. Results The proband of pedigree A manifested short stature, relative macrocephaly, mild flat nasal bridge, low‐set ears, short neck, and short thumbs. The proband of pedigree B had short height, abnormal vertebral development, and central precocious puberty. By trio‐based whole exome sequencing and in silico analyses, we identified two de novo heterozygous variants of ACAN: NM_013227.4: c.116dupT, p.Arg40Glufs51 and NM_013227.4: c.2367delC, p.Ser790Glnfs20 (accession number: AC103982.10). Conclusion The clinical manifestations of ACAN gene variants are diverse. ACAN gene variants are important genetic factors for short stature and should be considered as the differential diagnosis of children with idiopathic short stature (ISS).
format	article
author	Ming Wei Yanqin Ying Zhuxi Li Ying Weng Xiaoping Luo
author_facet	Ming Wei Yanqin Ying Zhuxi Li Ying Weng Xiaoping Luo
author_sort	Ming Wei
title	Identification of novel ACAN mutations in two Chinese families and genotype–phenotype correlation in patients with 74 pathogenic ACAN variations
title_short	Identification of novel ACAN mutations in two Chinese families and genotype–phenotype correlation in patients with 74 pathogenic ACAN variations
title_full	Identification of novel ACAN mutations in two Chinese families and genotype–phenotype correlation in patients with 74 pathogenic ACAN variations
title_fullStr	Identification of novel ACAN mutations in two Chinese families and genotype–phenotype correlation in patients with 74 pathogenic ACAN variations
title_full_unstemmed	Identification of novel ACAN mutations in two Chinese families and genotype–phenotype correlation in patients with 74 pathogenic ACAN variations
title_sort	identification of novel acan mutations in two chinese families and genotype–phenotype correlation in patients with 74 pathogenic acan variations
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/c83e253187934bb6bac6f6dd419ebd92
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Identification of novel ACAN mutations in two Chinese families and genotype–phenotype correlation in patients with 74 pathogenic ACAN variations

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