FGF10 missense mutations in aplasia of lacrimal and salivary glands (ALSG)

Aplasia of lacrimal and salivary glands (ALSG) is an autosomal dominant congenital anomaly characterized by aplasia, atresia or hypoplasia of the lacrimal and salivary systems. Affected individuals present with irritable eyes and dryness of the mouth with variable expressivity. Mutations in FGF10 were recently described in ALSG and in lacrimo-auriculo-dento-digital (LADD) syndrome which are overlapping clinical entities. We present here two families with ALSG associated with missense mutations (R80S and G138E, respectively) affecting highly conserved residues in FGF10. The clinical features of these patients further broaden the knowledge of FGF10-related phenotypes.     

Townes-Brocks syndrome: twenty novel SALL1 mutations in sporadic and familial cases and refinement of the SALL1 hot spot region

Townes-Brocks syndrome (TBS) is an autosomal dominant malformation syndrome characterized by renal, anal, ear, and thumb anomalies caused by SALL1 mutations. To date, 36 SALL1 mutations have been described in TBS patients. All but three of those, namely p.R276X, p.S372X, and c.1404dupG, have been found only in single families thereby preventing phenotype-genotype correlations. Here we present 20 novel mutations (12 short deletions, five short duplications, three nonsense mutations) in 20 unrelated families. We delineate the phenotypes and report previously unknown ocular manifestations, i.e. congenital cataracts with unilateral microphthalmia. We show that 46 out of the now 56 SALL1 mutations are located between the coding regions for the glutamine-rich domain mediating SALL protein interactions and 65 bp 3' of the coding region for the first double zinc finger domain, narrowing the SALL1 mutational hotspot region to a stretch of 802 bp within exon 2. Of note, only two SALL1 mutations would result in truncated proteins without the glutamine-rich domain, one of which is reported here. The latter is associated with anal, ear, hand, and renal manifestations, indicating that the glutamine-rich domain is not required for typical TBS.     

Extent of error in estimating nutrient intakes from food tables versus laboratory estimates of cooked foods

Individual cooked foods (104) and composite meals (92) were examined for agreement between nutritive value estimated by indirect analysis (E) (Indian National database of nutrient composition of raw foods, adjusted for observed moisture contents of cooked recipes), and by chemical analysis in our laboratory (M). The extent of error incurred in using food table values with moisture correction for estimating macro as well as micronutrients at food level and daily intake level was quantified. Food samples were analyzed for contents of iron, zinc, copper, beta-carotene, riboflavin, thiamine, ascorbic acid, folic acid and also for macronutrients, phytate and dietary fiber. Mean percent difference in energy content between E and M was 3.07+/-0.6%, that for protein was 5.3+/-2.0%, for fat was 2.6+/-1.8% and for carbohydrates was 5.1+/-0.9%. Mean percent difference in vitamin contents between E and M ranged from 32 (vitamin C) to 45.5% (beta-carotene content); and that for minerals between 5.6 (copper) to 19.8% (zinc). Percent E/M were computed for daily nutrient intakes of 264 apparently healthy adults. These were observed to be 108, 112, 127 and 97 for energy, protein, fat and carbohydrates respectively. Percent E/M for their intakes of copper (102) and beta-carotene (114) were closer to 100 but these were very high in the case of zinc (186), iron (202), and vitamins C (170), thiamine (190), riboflavin (181) and folic acid (165). Estimates based on food composition table values with moisture correction show macronutrients for cooked foods to be within +/- 5% whereas at daily intake levels the error increased up to 27%. The lack of good agreement in the case of several micronutrients indicated that the use of Indian food tables for micronutrient intakes would be inappropriate.     

Quinidine in the treatment of KCNT1‐positive epilepsies

We report 2 patients with drug‐resistant epilepsy caused by KCNT1 mutations who were treated with quinidine. Both mutations manifested gain of function in vitro, showing increased current that was reduced by quinidine. One, who had epilepsy of infancy with migrating focal seizures, had 80% reduction in seizure frequency as recorded in seizure diaries, and partially validated by objective seizure evaluation on EEG. The other, who had a novel phenotype, with severe nocturnal focal and secondary generalized seizures starting in early childhood with developmental regression, did not improve. Although quinidine represents an encouraging opportunity for therapeutic benefits, our experience suggests caution in its application and supports the need to identify more targeted drugs for KCNT1 epilepsies. Ann Neurol 2015;78:995–999     

External beam radiation therapy for PTFE dialysis grafts: a pilot study

Purpose: The aim of this study was to identify the effects of external beam radiation on PTFE dialysis graft dysfunction. Methods: Seven patients who underwent PTFE dialysis graft angioplasty were randomized to receive either two 8 Gy doses of external beam radiation or no radiation. The primary endpoint was time to graft thrombosis with a secondary endpoint of time to first intervention. Results: There was no statistically significant difference between the two groups in either of the endpoints, although grafts in the radiation group had a shorter time to thrombosis or intervention. Conclusions: Our results demonstrate technical feasibility for use of external beam radiation in the setting of dialysis vascular access graft dysfunction. Larger randomized studies are required to identify whether there is a clinical benefit from this intervention.