ABCMdb

PMID: 16429425

Mussaffi H, Prais D, Mei-Zahav M, Blau H
Cystic fibrosis mutations with widely variable phenotype: the D1152H example.
Pediatr Pulmonol. 2006 Mar;41(3):250-4., [PubMed]

Sentences

No. Mutations Sentence Comment

1 ABCC7 p.Asp1152His D1152H is a type IV cystic fibrosis transmembrane regulator (CFTR) mutation associated with abnormal chloride gating. Login to comment 4 ABCC7 p.Asp1152His Nine patients of varied Jewish ethnic origins were homozygous (2 patients) or compound heterozygous for D1152H with 11 of 182 potential alleles (6%). Login to comment 15 ABCC7 p.Asp1152His Although asymptomatic at times, the D1152H mutation is associated with a broad clinical spectrum. Login to comment 22 ABCC7 p.Asp1152His ß 2006 Wiley-Liss, Inc. Key words: cystic fibrosis; genetic counseling; phenotype; atypical CF; D1152H; pancreatic sufficient. Login to comment 25 ABCC7 p.Asp1152His ABCC7 p.Asp1152His In cases where testing reveals CFTR mutations associated with a variable phenotype, prenatal counseling is fraught with difficulties and must be based on maximal information regarding possible clinical scenarios.6 The D1152H mutation is associated with residual CFTR function and abnormal chloride gating, making it a typeIV CFmutation.7 Since 2000, it has been includedin routine prenatal and carrier genetic screening in Israel,8 and for various ethnic groups in the United States.9,10 Descriptions of clinical disease, first published in 1992,11 have been limited mainly to a congenital bilateral absence of the vas deferens (CBAVD)12 and late-onset mild disease, with almost normal sweat chloride values.13 Interestingly, D1152H was found in 6.27% of referrals for carrier screening among Hispanics, while the disease 1 Kathy and Lee Graub Cystic Fibrosis Center and Pulmonary Unit, Schneider Children`s Medical Center of Israel, Petah Tikva, Israel. Login to comment 31 ABCC7 p.Asp1152His Our experience contrasts markedly with published observations regarding clinical disease associated with the D1152H mutation. Login to comment 36 ABCC7 p.Asp1152His All other patients included in the analysis met the criteria for diagnosis of CF as proposed by the statement of the CF Foundation Consensus Panel.4 Patients who were either homozygous or compound-heterozygous for the D1152H mutation were identified. Login to comment 43 ABCC7 p.Asp1152His In children, percent ideal body weight was calculated, with !90% considered a normal nutritional state.15 RESULTS Of 91 patients reviewed, 9 (10%) were either homozygous or heterozygous for the D1152H mutation, with a total of 11/182 alleles (6%). Login to comment 51 ABCC7 p.Asp1152His The last 4 patients described were all infants, diagnosed due to pulmonary symptoms despite pancreatic sufficiency (patients 6 and 7), dilated bowel loops on fetal ultrasound (patient 8), or the recent introduction of D1152H in prenatal genetic tests (patient 9). Login to comment 53 ABCC7 p.Asp1152His ABCC7 p.Asp1152His Although this feature suggested the possibility of meconium ileus and a more severe CF phenotype, the TABLE 1-Demographics, Genotype, Sweat Chloride, and Mode of Presentation of D1152H Subjects1 Patient no. Login to comment 54 ABCC7 p.Trp1282* ABCC7 p.Trp1282* ABCC7 p.Asp1152His ABCC7 p.Asp1152His Age (y)/gender Age (y) at diagnosis Ethnic origin (all Jewish) Other CF mutation Sweat ClÀ (meq/l)2 Presentation 1 54/m 46 Ashkenazi W1282X 120 Bronchiectasis 2 39/m 33 Turkey/Iraq D1152H 49 CBAVD 3 46/f 41 Ashkenazi DF508 54 Bronchiectasis 4 49/m 44 Ashkenazi DF508 113 Bronchiectasis 5 51/f 49 Ashkenazi DF508 50 Pancreatitis 6 1.5/m 0.5 Iran/Turkey/Bulgaria D1152H 53 Lung disease 7 2/m 1.3 Iran/Bulgaria W1282X 70 Lung disease 8 1/f Prenatal Ashkenazi DF508 80 Prenatal dilated bowel 9 0.8/m Prenatal Tunis/Ashkenazi DF508 28 Prenatal screening 1 Patients 4 and 5 are siblings. Login to comment 87 ABCC7 p.Asp1152His DISCUSSION In this paper, we describe 9 CF patients carrying the D1152H mutation, in a clinic of 91 patients from infancy to 56 years, at the Graub CF Center (Schneider Children`s Medical Center of Israel). Login to comment 89 ABCC7 p.Asp1152His The D1152H mutation was first described in 1992,11 and was included in the screening panels of major laboratories testing Jewish populations since the year 2000. Login to comment 92 ABCC7 p.Asp1152His Based on previous case reports of mild phenotype, the Israel Medical Genetic Organization recently decided not to include this mutation in the panel tested in the carrier-screening program.16 In contrast to the above, the prevalence of D1152H in our clinic population clearly demonstrates that this mutation is associated with significant though atypical clinical disease. Login to comment 93 ABCC7 p.Asp1152His Comparing 148 potential alleles in our clinic`s 74 Jewish patients, 12 (8%) were D1152H. Login to comment 97 ABCC7 p.Asp1152His Undoubtedly, a multicenter analysis of clinical pictures associated with the D1152H mutation is needed. Login to comment 102 ABCC7 p.Asp1152His Thenatural historyofinfants withthe D1152H mutation is unknown, and some of our adult patients describe pulmonary symptoms from early childhood for which they received no specific CF treatment. Login to comment 105 ABCC7 p.Asp1152His Pancreatic sufficiency appears to be the most constant feature of young patients with D1152H mutations. Login to comment 112 ABCC7 p.Asp1152His The cardinal importance of this series description is to enable more informed genetic counseling for carriers of the D1152H mutation and in the prenatal setting. Login to comment 116 ABCC7 p.Asp1152His Subjects with the D1152H mutation are an example of an ever-increasing population of patients with atypical CF. Login to comment