Fanny Cortés

National food-fortification program with folic acid in Chile.

The Chilean Ministry of Health legislated to add folic acid (2.2 mg/100 g) to wheat flour to reduce the risk of neural tube defects (NTD), beginning in January 2000. This policy resulted in a significant increase in serum and red blood cell folate in women of childbearing age 1 year after fortification. The frequency of NTD was studied in all births, both live and stillbirths, in a prospective hospital-based design including 25% of national births during 1999–2000 (prefortification period) and 2001–2002 (postfortification period). During the prefortification period, there was a total of 120,566 newborns, and the NTD rate was 17.1/10,000 births. During the postfortification period (2001–2002) there was a total of 117,704 newborns, and the NTD rate was significantly reduced by 43% to 9.7/10,000 births (RR = 0.57; 95% CI, 0.45 to 0.71). This implies a reduction of 43% in the rate of NTD. The costs per NTD case and infant death averted were 1,200 international dollars (I

Wheat flour fortification with folic acid: Changes in neural tube defects rates in Chile†

) and I

High Incidence of Noonan Syndrome Features Including Short Stature and Pulmonic Stenosis in Patients carrying NF1 Missense Mutations Affecting p.Arg1809: Genotype–Phenotype Correlation

11,000, respectively. The cost per disability-adjusted life year (DALY) averted was I

A frameshift insertion in the cone cyclic nucleotide gated cation channel causes complete achromatopsia in a consanguineous family from a rural isolate

91, or 0.8% of the countrys per capita GDP. On the overall, fortification resulted in net cost savings of I

Adrenarche in Prader-Willi syndrome appears not related to insulin sensitivity and serum adiponectin.

1.8 million. Fortification of wheat flour with folic acid has proven to be an effective and cost saving strategy for the primary prevention of NTD in a middle-income country in a postepidemiological transition, and in a dramatically short period of time.

Gemelas con autismo y retardo mental asociado a translocacion cromosomica balanceada (7;20)

In January 2000, Chilean Ministry of Health mandated the addition of folic acid (FA) to wheat flour in order to reduce the risk of neural tube defects (NTDs). This policy resulted in significant increases in serum and red cell folate in women of fertile age 1 year after fortification. To evaluate the effect of wheat flour fortification on the prevalence of NTDs in Chile we designed a prospective hospital‐based surveillance program to monitor the frequency of NTDs in all births (live and stillbirths) with birth weight ≥500 g at the nine public maternity hospitals of Santiago, Chile from 1999 to 2009. During the pre‐fortification period (1999–2000) the NTD rate was 17.1/10,000 births in a total of 120,566 newborns. During the post‐fortification period (2001–2009) the NTD rate decreased to 8.6/10,000 births in a total of 489,915 newborns, which translates into a rate reduction of 50% (RR: 0.5; 95% CI: 0.42–0.59) for all NTDs. The rate reduction by type of NTD studied was: 50% in anencephaly (RR: 0.5; 95% CI: 0.38–0.67), 42% in cephalocele (RR: 0.58; 95% CI: 0.37–0.89), and 52% in spina bifida (RR: 0.48; 95% CI: 0.38–0.6). Rates showed significant reduction both in stillbirths and live births: 510.3 to 183.6/10,000 (RR = 0.36; 95% CI: 0.25–0.53) and 13.3 to 7.5/10,000 (RR = 0.56; 95% CI: 0.47–0.68), respectively. In Chile, fortification of wheat flour with FA has proven to be an effective strategy for the primary prevention of NTDs.

Five Novel RPGR Mutations in Families with X- Linked Retinitis Pigmentosa

Neurofibromatosis type 1 (NF1) is one of the most frequent genetic disorders, affecting 1:3,000 worldwide. Identification of genotype–phenotype correlations is challenging because of the wide range clinical variability, the progressive nature of the disorder, and extreme diversity of the mutational spectrum. We report 136 individuals with a distinct phenotype carrying one of five different NF1 missense mutations affecting p.Arg1809. Patients presented with multiple café‐au‐lait macules (CALM) with or without freckling and Lisch nodules, but no externally visible plexiform neurofibromas or clear cutaneous neurofibromas were found. About 25% of the individuals had Noonan‐like features. Pulmonic stenosis and short stature were significantly more prevalent compared with classic cohorts (P < 0.0001). Developmental delays and/or learning disabilities were reported in over 50% of patients. Melanocytes cultured from a CALM in a segmental NF1‐patient showed two different somatic NF1 mutations, p.Arg1809Cys and a multi‐exon deletion, providing genetic evidence that p.Arg1809Cys is a loss‐of‐function mutation in the melanocytes and causes a pigmentary phenotype. Constitutional missense mutations at p.Arg1809 affect 1.23% of unrelated NF1 probands in the UAB cohort, therefore this specific NF1 genotype–phenotype correlation will affect counseling and management of a significant number of patients.

Barber-Say syndrome: further delineation of the clinical spectrum

Complete achromatopsia is genetically heterogeneous and segregates with mutations in CNGA3 or CNGB3 genes, which respectively encode for α- and β-subunits of the cyclic-nucleotide-gated (CNG) cation channel expressed in cone photoreceptors. High incidence of the disease (1 in 60) was detected in a rural isolate in central Chile. We excluded previously reported mutations in a consanguineous kindred with five affected members. Genotype analysis with short tandem repeat polymorphic (STRP) markers provided evidence to search for the causative mutation in CNGB3. Two sequence variations, c.492_493insT and c.488A>G, flanking an adenosine (A5) repeat in exon 4 were identified. The frameshift mutation creates two consecutive stop codons in exon 5 that would induce premature translation termination. The severely truncated β-subunit is likely to render a nonfunctional cone CNG channel and cause total colour blindness in this kindred.

Búsqueda de afecciones genéticas como etiología de déficit intelectual en individuos que asisten a escuelas de educación especial

Prader-Willi syndrome (PWS) is a genetic disorder characterized by dysmorphic features, obesity, hypogonadism, hypotonia and mental retardation. Obesity has been linked to insulin resistance and the latter has also been associated with premature adrenarche. Since up to date a controlled study to investigate adrenarche and its hormonal regulation was lacking in PWS, our aim was to assess whether prepubertal PWS patients develop premature adrenarche and its relationship with markers of insulin sensitivity. Fourteen prepubertal children with PWS (6 M, 8 F) and 10 non-syndromal simple obese matched controls (5 M, 5 F) participated (mean age: 7.62 ± 1.84 years). A fasting blood sample was obtained for adrenal and ovarian androgens, sex hormone binding globulin, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-1, leptin, adiponectin and a lipid profile. Thereafter an oral glucose tolerance test was performed. PWS patients were smaller at birth and a higher proportion displayed premature pubarche. No differences were found in testosterone, androstenedione, sex hormone binding globulin, free androgen index, homeostatic model assessment-IR, 2-hour insulin, leptin or adiponectin levels. 17-hydroxyprogesterone and DHEAS levels however, were significantly higher in PWS. IGF-I levels were significantly lower in PWS and correlated significantly with height SDS (p < 0.05). In conclusion, a higher proportion of premature adrenarche in our PW patients was observed, which was not explained by differences in insulin sensitivity or plasma levels of adipokines and IGF-I.

GROWTH DELAY IN SCHOOL AGE CHILDREN OF LOW SOCIOECONCMIC LEVEL: ITS IMPACT ON COGNITIVE FUNCTIONING.

A pair of female twins with mental retardation and autism are presented. In their study a balanced chromosomaltranslocation, involving chromosomes 7 and 20, was demonstrated. The association between mental retardation,autism and chromosomal anomalies is discussed.(Key words: Mental retardation, autism, balanced chromosomal translocation, identical twins).