Tags

Type your tag names separated by a space and hit enter

A novel homozygous initiation codon variant associated with infantile alpha-Bcrystallinopathy in a Chinese family.
Mol Genet Genomic Med 2019; 7(8):e825MG

Abstract

BACKGROUND

Due to inconsistencies with reported myofibrillar myopathy (MFM), including autosomal dominant inheritance, late onset and a slowly progressive course, the severe, recessively inherited form of CRYAB (alpha-B crystallin) gene-related infantile MFM has been suggested. Here, we report an infant in a Chinese family with fatal neonatal-onset hypertonic MFM with a novel CRYAB homozygous variant (c.3G > A (p.Met1?)).

METHODS

Muscle biopsy indicated that muscle fibers showed a uniformly small diameter, cell atrophy, and visible focal muscle fiber degeneration and necrosis consistent with myogenic myopathy. We performed the whole exome sequencing of pathogenic genes and identified it as MFM.

RESULTS

The proband presented with profound muscle stiffness, progressive respiratory distress and a concurrent abnormal increase in myocardial enzymogram, and the patient died in the 17th month of life. Muscle biopsy and electron microscopy results were consistent with ultramicroscopic myogenic damage and pathological changes. Mutation analysis of the proband identified a novel rare homozygous mutation in the initiation codon of the CRYAB gene, which was inherited from currently asymptomatic, heterozygous carrier parents, and his heterozygous biological brother is unaffected.

CONCLUSIONS

This article reports one infant with CRYAB-related neonatal onset MFM with a novel homozygous variant in CRYAB. To our knowledge, this is the first reported case of infantile alpha-Bcrystallinopathy in the Chinese population.

Authors+Show Affiliations

Department of Neonates, Dongguan Children's Hospital, Dongguan, China. Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, China.Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, China. Medical Laboratory, Dongguan Children's Hospital, Dongguan, China.Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.Department of Neonates, Dongguan Children's Hospital, Dongguan, China. Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, China.Department of Neonates, Dongguan Children's Hospital, Dongguan, China. Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, China.Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, China. Medical Laboratory, Dongguan Children's Hospital, Dongguan, China.Department of Neonates, Dongguan Children's Hospital, Dongguan, China. Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, China.Department of Medical and Molecular Genetics, Dongguan Institute of Pediatrics, Dongguan, China. Medical Laboratory, Dongguan Children's Hospital, Dongguan, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31215171

Citation

Ma, Keze, et al. "A Novel Homozygous Initiation Codon Variant Associated With Infantile alpha-Bcrystallinopathy in a Chinese Family." Molecular Genetics & Genomic Medicine, vol. 7, no. 8, 2019, pp. e825.
Ma K, Luo D, Tian T, et al. A novel homozygous initiation codon variant associated with infantile alpha-Bcrystallinopathy in a Chinese family. Mol Genet Genomic Med. 2019;7(8):e825.
Ma, K., Luo, D., Tian, T., Li, N., He, X., Rao, C., ... Lu, X. (2019). A novel homozygous initiation codon variant associated with infantile alpha-Bcrystallinopathy in a Chinese family. Molecular Genetics & Genomic Medicine, 7(8), pp. e825. doi:10.1002/mgg3.825.
Ma K, et al. A Novel Homozygous Initiation Codon Variant Associated With Infantile alpha-Bcrystallinopathy in a Chinese Family. Mol Genet Genomic Med. 2019;7(8):e825. PubMed PMID: 31215171.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel homozygous initiation codon variant associated with infantile alpha-Bcrystallinopathy in a Chinese family. AU - Ma,Keze, AU - Luo,Dong, AU - Tian,Tian, AU - Li,Ning, AU - He,Xiaoguang, AU - Rao,Chunbao, AU - Zhong,Baimao, AU - Lu,Xiaomei, Y1 - 2019/06/18/ PY - 2019/02/28/received PY - 2019/05/22/revised PY - 2019/05/29/accepted PY - 2019/6/20/pubmed PY - 2019/6/20/medline PY - 2019/6/20/entrez KW - CRYAB KW - Chinese KW - infant KW - muscle performance KW - myofibrillar myopathy SP - e825 EP - e825 JF - Molecular genetics & genomic medicine JO - Mol Genet Genomic Med VL - 7 IS - 8 N2 - BACKGROUND: Due to inconsistencies with reported myofibrillar myopathy (MFM), including autosomal dominant inheritance, late onset and a slowly progressive course, the severe, recessively inherited form of CRYAB (alpha-B crystallin) gene-related infantile MFM has been suggested. Here, we report an infant in a Chinese family with fatal neonatal-onset hypertonic MFM with a novel CRYAB homozygous variant (c.3G > A (p.Met1?)). METHODS: Muscle biopsy indicated that muscle fibers showed a uniformly small diameter, cell atrophy, and visible focal muscle fiber degeneration and necrosis consistent with myogenic myopathy. We performed the whole exome sequencing of pathogenic genes and identified it as MFM. RESULTS: The proband presented with profound muscle stiffness, progressive respiratory distress and a concurrent abnormal increase in myocardial enzymogram, and the patient died in the 17th month of life. Muscle biopsy and electron microscopy results were consistent with ultramicroscopic myogenic damage and pathological changes. Mutation analysis of the proband identified a novel rare homozygous mutation in the initiation codon of the CRYAB gene, which was inherited from currently asymptomatic, heterozygous carrier parents, and his heterozygous biological brother is unaffected. CONCLUSIONS: This article reports one infant with CRYAB-related neonatal onset MFM with a novel homozygous variant in CRYAB. To our knowledge, this is the first reported case of infantile alpha-Bcrystallinopathy in the Chinese population. SN - 2324-9269 UR - https://www.unboundmedicine.com/medline/citation/31215171/A_novel_homozygous_initiation_codon_variant_associated_with_infantile_alpha-Bcrystallinopathy_in_a_Chinese_family L2 - https://doi.org/10.1002/mgg3.825 DB - PRIME DP - Unbound Medicine ER -