ABCMdb

PMID: 7513296

Boteva K, Papageorgiou E, Georgiou C, Angastiniotis M, Middleton LT, Constantinou-Deltas CD
Novel cystic fibrosis mutation associated with mild disease in Cypriot patients.
Hum Genet. 1994 May;93(5):529-32., [PubMed]

Sentences

No. Mutations Sentence Comment

21 ABCC7 p.Leu346Pro Here we report on the identification of a novel mutation, L346P, in two unrelated Cypriot patients with mild symptomatology. Login to comment 39 ABCC7 p.Gly551Asp ABCC7 p.Trp1282* ABCC7 p.Arg553* ABCC7 p.Gly542* ABCC7 p.Arg1283Met Those mutations were 621+lG>T, G542X, G551D, R553X, W1282X and R1283M, and the methodology used is the Amplification Refractory Mutation System (Newton et al. 1989). Login to comment 42 ABCC7 p.Leu346Pro ABCC7 p.Leu346Pro Symptoms of characterized patients Patient 4457 Patient 5292 (L346P/AF508) (L346P/1677delTA) - No meconium ileus at birth - No gastrointestinalproblems - No pancreatic insufficiency - Sweat tests of 55 and 78 MEq/1 - Occasional electrolyte disturbances (mostly in summer as dehydration) - Some chest infectionsa - Failure to thrive - No meconium ileus at birth - One incidence of gastrointestinalproblems (vomiting, diarrhoea) - No pancreatic insufficiency - Negative sweat test - Occasional electrolyte disturbances - No lung involvement - Slight physical growth delay aNot unusuallyfrequent consideringthat this patient was born with transposition of the great arteries, for which he was operated on in the neonatal period Fig. 1. Login to comment 44 ABCC7 p.Leu346Pro Members of the families that carry the L346P mutation are shown. Login to comment 54 ABCC7 p.Leu346Pro ABCC7 p.Leu346Pro This transition results in the substitution of proline for leucine at residue 346 (L346P), and it introduces a new restriction site for BstUI. Login to comment 65 ABCC7 p.Leu346Pro Patient with DNA no. 5292 was first identified as a carrier of 1677delTA, Here it is shown that patients 4457 and 5292 are both also heterozygous for L346P. Login to comment 70 ABCC7 p.Leu346Pro Detection of mutation L346P by PCR-restriction digestion. Login to comment 78 ABCC7 p.Leu346Pro Also shown is that the sister of 4457 in family 2801 (4460), is heterozygous for L346P population (Constantinou-Deltas et al. 1992), whereas in mainland Greece one expects 1 AF508 chromosome in 110 (Balassopoulou et al. 1990). Login to comment 86 ABCC7 p.Arg347Pro ABCC7 p.Leu346Glu These milder phenotypes are more easily explained by the possible mildness of the second mutation, L346E This is in exon 7, which is part of the membrane-spanning region, and next to another previously reported mutation, R347P, which is also known to be associated with less severely impaired pancreatic function (Dean et al. 1990). Login to comment 89 ABCC7 p.Leu346Pro Hence, in our patients this is probably the case, with L346P dominant to AF508 and 1677delTA. Login to comment 90 ABCC7 p.Leu346Pro It is interesting that L346P was found in two unrelated families, and this raises the possibility that other mildly affected patients carry this Cypriot mutation. Login to comment