✦ LIBER ✦

Four new cases of lethal osteogenesis imperfecta due to glycine substitutions in COL1A1 and genes

✍ Scribed by Monica Mottes; Macarena Gomez Lira; Francesca Zolezzi; Maurizia Valli; Veronica Lisi; Peter Freising

Publisher: John Wiley and Sons
Year: 1998
Tongue: English
Weight: 34 KB
Volume: 12
Category: Article
ISSN: 1059-7794
DOI: 10.1002/(sici)1098-1004(1998)12:1<71::aid-humu16>3.0.co;2-4

No coin nor oath required. For personal study only.

✦ Synopsis

Perinatal lethal osteogenesis imperfecta (OMIM# 166210) is the result of heterozygous mutations of the COL1A1 and COL1A2 genes. Here we describe the molecular defects responsible for four cases of lethal OI. Two glycine substitutions within the COL1A1 gene (G478S, G994D) and two glycine substitutions within the COL1A2 gene (G319V, G697C) were identified. The mutation sites were localized in proalpha2(I)and proalpha2(I)mRNA molecules, respectively, by chemical cleavage of mismatch in heteroduplex nucleic acids. Subsequent reverse transcription-PCR amplification, cloning and sequencing, led to mutation identification. The aminoacid substitutions were due to two G->A transitions in COL1A1(cases 1,2), to a G->T transversion in COL1A2 (case 3), and to two contiguous point mutations in COL1A2 (case 4). All five nucleotide changes appeared to be fresh mutations.

COL1A1(accession number Z74615) and COL1A2 (accession number Z74616) wild type coding sequences (cDNA) were deduced from the EMBL DNA sequence database.

The mutations described here can also be found in the human type I collagen mutation database

📜 SIMILAR VOLUMES

Two new recurrent nucleotide mutations i

Two new recurrent nucleotide mutations in the COL1A1 gene in four patients with osteogenesis imperfecta: About one-fifth are recurrent

✍ Jarmo Körkkö; Helena Kuivaniemi; Petteri Paassilta; Jiapiao Zhuang; Gerard Tromp 📂 Article 📅 1997 🏛 John Wiley and Sons 🌐 English ⚖ 239 KB 👁 1 views

Previous observations on mutations causing osteogenesis imperfecta (0I) suggested that unrelated patients had private mutations. Here preliminary studies on two patients with type I OI indicated that some mutations in the COL1A1 gene for type I procollagen cannot be detected by analyses of cDNAs. Th

Substitution of arginine for glycine at

Substitution of arginine for glycine at position 154 of the α1 chain of type I collagen in a variant of osteogenesis imperfecta: Comparison to previous cases with the same mutation

✍ Zhuang, Jiapiao; Tromp, Gerard; Kuivaniemi, Helena; Castells, Salvador; Prockop, 📂 Article 📅 1996 🏛 John Wiley and Sons 🌐 English ⚖ 33 KB 👁 1 views

A substitution of arginine for glycine at amino acid position 154 of the al(1) collagen chain was found in a father and his three children. The phenotype of the patients includes manifestations of types I and IIUIV osteogenesis imperfecta, but appears to be milder than that of the previously describ

A new case of pyruvate dehydrogenase def

A new case of pyruvate dehydrogenase deficiency due to a novel mutation in the pdx1 gene

✍ Runu Dey; Manuele Mine; Isabelle Desguerre; Abdelhamid Slama; Loic Van Den Bergh 📂 Article 📅 2003 🏛 John Wiley and Sons 🌐 English ⚖ 175 KB 👁 2 views

Identification of a new heterozygous poi

Identification of a new heterozygous point mutation in the COL1A2 gene leading to skipping of exon 9 in a patient with joint laxity, hyperextensibility of skin and blue sclerae

✍ Sergej Feshchenko; Jürgen Brinckmann; Hartwig W. Lehmann; Hans-Georg Koch; Peter 📂 Article 📅 1998 🏛 John Wiley and Sons 🌐 English ⚖ 52 KB 👁 2 views

A heterozygous deletion of exon 9 in the COL1A2 -mRNA of a patient with symptoms of both the Ehlers -Danlos -Syndrome and the Osteogenesis Imperfecta is described. In the genomic DNA of the patient, exon 9 is homozygously present. We identified a novel heterozygous point mutation in the splice donor