Identification of a novel mutation (A268G) in exon 8 of the HTRβ gene in a large family with thyroid hormone resistance

✍ Scribed by Pascal Jézéquel; Isabelle Guilhem; Jean Pierre Hespel; André Le Treut; Jean Yves Le Gall; Hubert Allannic; Martine Blayau

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 135 KB
• Volume: 8
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/(sici)1098-1004(1996)8:4<396::aid-humu24>3.0.co;2-x

✦ Synopsis

MUTATION NOTES

PCR-SSCP and the protein truncation test (PTT), which utilises in v i m transcription-translation to detect mutations that result in the introduction of a permature stop codon and thus to a truncated protein (van der Luijt et al., 1994). Exons 1-14 of the APC gene were PCR amplified using the primers described by , and PCR products were separated on 6% polyacrylamide gels (acrylamide: bis 49:l) at 4°C following denaturation of PCR products. Exon 15 of the APC gene was screened for mutations using the technique of FIT with the primers described by . Exons showing abnormal SSCP patterns were reamplified and sequenced directly; samples showing truncated proteins in the PTT test were also reamplified and sequenced directly. Mutations were confirmed by their presence in all available affected individuals of the kindred as determined by direct sequencing.

In kindred "A", a single base deletion at codon 1362 (TCC-CC) in exon 15, causing a frameshift, was identified. This results in a premature stop codon 156 nucleotides further downstream. In kindred "B', a single base deletion at codon 592 (lTA-+TA) in exon 14 was identified resulting in a premature stop codon 50 nucleotides down-stream. In kindred "C", a single base C-G substitution was identified at codon 159 in exon 4 (TAC-+TACi) resulting in a T v S t o p mutation. Mutations in exon 4 have been associated with a milder form of APC known as attenuated adenomatous polyposis coli (AAPC), characterised by fewer colonic polyps, a phenotype also exhibited by affected members of kindred "C".