ABCMdb

PMID: 22310382

Diana A, Tesse R, Polizzi AM, Santostasi T, Manca A, Leonetti G, Seia M, Porcaro L, Cavallo L
A large deletion causes apparent homozygosity for the D1152H mutation in the cystic fibrosis transmembrane regulator (CFTR) gene.
Gene. 2012 Apr 10;497(1):90-2. Epub 2012 Jan 31., [PubMed]

Sentences

No. Mutations Sentence Comment

0 ABCC7 p.Asp1152His ABCC7 p.Asp1152His Short Communication A large deletion causes apparent homozygosity for the D1152H mutation in the cystic fibrosis transmembrane regulator (CFTR) gene Anna Diana a, ⁎,1 , Riccardina Tesse a,1 , Angela M. Polizzi a , Teresa Santostasi a , Antonio Manca a , Giuseppina Leonetti a , Manuela Seia b , Luigi Porcaro b , Luciano Cavallo a a Department of Biomedicine of the Developing Age, Apulian Referral Center for Cystic Fibrosis, Policlinico, University of Bari, Bari, Italy b Medical Genetics Laboratory, Fondazione IRCCS Policlinico, Mangiagalli, Regina Elena, Milan, Italy a b s t r a c ta r t i c l e i n f o Article history: Accepted 21 January 2012 Available online 31 January 2012 Keywords: CFTR Cystic fibrosis Homozygosis Large deletion Phenotype We report the case of a patient with an apparent homozygosity for the D1152H mutation located in exon 18 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Login to comment 3 ABCC7 p.Asp1152His Sequencing of the CFTR exon 18 together with quantitative genomic assays, such as real-time PCR and the multiplex ligation probe amplification (MLPA) techniques, were performed and revealed that the father was heterozygous for the D1152H mutation and the mother carried a large deletion of the CFTR gene encompassing the genomic sequence including the same mutation. Login to comment 4 ABCC7 p.Asp1152His The child inherited D1152H from his father and the large deletion of the CFTR gene from his mother. Login to comment 5 ABCC7 p.Asp1152His We suggest that D1152H likely acts as a mild mutation with a dominant effect on the severe deletion of exon 18, considering that after 3 years of clinical examinations the child shows no classical signs and symptoms of CF. Login to comment 19 ABCC7 p.Asp1152His We firstly report the case of a patient with an apparent homozygosity for the D1152H mutation located in exon 18 and commonly associated with a variable CF phenotype, in presence of a non compatible molecular analysis in his parents and a peculiar disease expression, investigated by specific genomic assays of CFTR rearrangements detection. Login to comment 29 ABCC7 p.Asp1152His The father resulted heterozygous for the D1152H mutation, while the mother apparently did not show any tested genetic variation for the CFTR gene. Login to comment 33 ABCC7 p.Asp1152His The genetic investigation of the newborn by RDB assay showed an apparent homozygosity for D1152H, not compatible with the parents' genetic status. Login to comment 34 ABCC7 p.Asp1152His To bear out the unexpected result, sequencing of the CFTR exon 18 was performed by means of the ABI Prism 310 (Applied Biosystems, Foster City, CA), confirming the homozygosity for D1152H in the child, the heterozygosity for the same mutation in his father and the wild-type status of his mother (Fig. 1). Login to comment 37 ABCC7 p.Asp1152His ABCC7 p.Asp1152His The second possibility was the hemizygosity of the proband bearing D1152H on one allele (inherited from father) and a large deletion of the CFTR gene encompassing the same sequence region, including D1152H, on the second allele (derived from mother). Login to comment 45 ABCC7 p.Asp1152His We describe for the first time a CF patient having D1152H/ dele17a-18 genotype with a history of hyperechogenic bowel loops and MI, but non classic form CF phenotype. Login to comment 52 ABCC7 p.Asp1152His The D1152H is a type IV CFTR mutation, which is associated with residual CFTR function and abnormal chloride gating (Vankeerberghen et al., 1998). Login to comment 54 ABCC7 p.Asp1152His D1152H is often associated with non classical forms of CF and it has been detected frequently in men with congenital bilateral absence of vas deferens (CBAVD) (Highsmith et al., 2005). Login to comment 55 ABCC7 p.Asp1152His In our case the D1152H is in compound heterozygosity with dele17a-18 (3120+1Kbdel8.6Kb) which was firstly described in Palestinian Arab CF patients with a severe CF phenotype (Lerer et al., 1999). Login to comment 58 ABCC7 p.Asp1152His Sequence electropherograms showing by continuous arrows the homozygosity for D1152H in exon 18 of CFTR gene in the proband (A), the heterozygosity for the same mutation in his father (B), and the wild-type status of his mother (C). Login to comment 62 ABCC7 p.Asp1152His We speculate that the D1152H, acting as a mild mutation, has a dominant effect on the severe dele17a-18. Login to comment 63 ABCC7 p.Gly542* ABCC7 p.Asp1152His ABCC7 p.Asp1152His We speculate that the D1152H, acting as a mild mutation, has a dominant effect on the severe dele17a-18. Login to comment 64 ABCC7 p.Gly542* ABCC7 p.Asp1152His ABCC7 p.Asp1152His Orgad et al. (2002) reported a case of hyperechogenic bowel loops and MI in a fetus carrying the combination of D1152H and G542X mutations, but they did not describe the clinical follow-up of the newborn. Login to comment 65 ABCC7 p.Asp1152His Moreover Yalçin et al. (2008) reported a 16-year-old boy with the rare 2183AA>G/D1152H genotype, presenting with MI in the neonatal period and a mild clinical phenotype later in life with no evidence of PI. Login to comment 67 ABCC7 p.Asp1152His Furthermore, we suggest the importance of the inclusion of D1152H mutation in the screening panel for CF diagnosis. Login to comment 68 ABCC7 p.Asp1152His Furthermore, we suggest the importance of the inclusion of D1152H mutation in the screening panel for CF diagnosis. Login to comment