We identified two families with an autosomal-recessive disorder manifested by severe enamel hypoplasia, delayed and failed tooth eruption, misshapen teeth, intrapulpal calcifications, and localized gingival hyperplasia. Genetic analyses identified novel FAM20A mutations associated with the disease phenotype in both families. The proband of Family 1 had an altered splice junction in Intron 1 (g.502011G>C; c.405-1G>C) and a missense mutation in Exon 8 (g.65094G>A; c.1207G>A; p.D403N). The missense mutation is notable because D403 is strictly conserved among FAM20A homologues, and the corresponding defect in FAM20C caused osteosclerotic bone dysplasia and a loss of kinase activity. The proband at age 12 yrs tested negative for nephrocalcinosis. The proband and her affected father in Family 2 were homozygous for a single nucleotide deletion that altered a splice junction in Intron 10 (g.66622del; c.1361+4del). Minigene analyses demonstrated that this alteration precluded normal splicing. Immunohistochemistry (IHC) of mouse maxillary first molars localized FAM20A in secretory-stage ameloblasts, in odontoblasts, and in the eruption pathway. IHC of kidneys localized FAM20A in the renal tubules. We conclude that FAM20A is likely a secretory pathway kinase and that loss-of-function mutations cause pathology where its phosphorylations are necessary for normal development or homeostasis.

Medullary thyroid carcinoma occurs in both sporadic (75%) and hereditary (25%) forms. The missense mutations of RET proto-oncogene in MTC development have been well demonstrated. To investigate the spectrum of predominant RET germline mutations in exons 10, 11, and 16 in hereditary MTC in Iranian population, 217 participants were included. Genomic DNAs were extracted from the leukocytes using the standard Salting Out/Proteinase K method. Mutation detection was performed through PCR-RFLP and DNA sequencing. In 217 participants, 43 missense mutations were identified in exons 10 (6%), 11 (13%), and 16 (0.9%). Moreover, a novel germline mutation was detected in exon 11 (S686N). Also four different polymorphisms were found in intron 16 in eight patients. The obtained data showed the frequency profile of RET mutations in Iranian individuals with MTC (19.8%). The most frequent mutation in our population was C634G whereas in most population it was C634R. Altogether, these results underline the importance of the genetic background of family members of any patient with MTC.

Background: The primary objective of the present study was to assess changes in the nutritional status and quality of life in acute leukaemia patients, aged ! 15 years, who had undergone induction chemotherapy. Methods: A preliminary and post-induction chemotherapy assessment of patients' nutritional status, quality of life, sociodemographic status and medical characteristics was conducted using the Patient Generated Subjective Global Assessment (PG-SGA) and the European Organization for Research and Treatment of Cancer quality of life (QOL-C30, version 3) questionnaires. The PG-SGA is a clinical nutrition assessment tool used to evaluate oncology patients. Patients with newly-diagnosed acute laeukaemia, aged ! 15 years, at three hospitals in Tehran (from May 2009 to March 2010), were recruited for the present study. Results: Sixty-three acute leukaemia patients [65% men and 35% women with a mean (SD) age of 33 (15.4) years] participated in the present study. A total of 19.4% were found to be malnourished prior to chemotherapy. After chemotherapy, 76.1% of patients were considered moderately malnourished, whereas 6.3% were severely malnourished. After induction chemotherapy, both the nutritional status and quality of life deteriorated in the majority of patients, as demonstrated by a paired t-test. Conclusions: A deteriorated nutritional status and quality of life was the result of the side effects posed by induction chemotherapy in the patients investigated in the present study. These findings highlight the need for an appropriate nutritional support programme to improve the nutritional status and quality of life in patients with leukaemia undergoing chemotherapy.