Uniparental disomy causes deficiencies of vitamin K-dependent proteins.

Essentials Vitamin K-dependent coagulant factor deficiency (VKCFD) is a rare autosomal recessive disorder. We describe a case of inherited VKCFD due to uniparental disomy. The homozygous mutation caused the absence of GGCX isoform 1 and overexpression of Δ2GGCX. Hepatic and non-hepatic vitamin K-dependent proteins must be assayed to monitor VKCFD treatment. SUMMARY: Background Inherited deficiency of all vitamin K-dependent coagulant factors (VKCFD) is a rare autosomal recessive disorder caused by mutations in the γ-glutamyl carboxylase gene (GGCX) or the vitamin K epoxide reductase gene (VKORC1), with great heterogeneity in terms of both clinical presentation and response to treatment. Objective To characterize the molecular basis of VKCFD in a Spanish family. Methods and Results Sequencing of candidate genes, comparative genomic hybridization and massive sequencing identified a new mechanism causing VKCFD in the proband. Uniparental disomy (UPD) of chromosome 2 caused homozygosity of a mutation (c.44-1G>A) resulting in aberrant GGCX splicing. This change contributed to absent expression of the mRNA coding for the full-length protein, and to four-fold overexpression of the smaller mRNA isoform lacking exon 2 (Δ2GGCX). Δ2GGCX might be responsible for two unexpected clinical observations in the patient: (i) increased plasma osteocalcin levels following vitamin K1 supplementation; and (ii) a mild non-bleeding phenotype. Conclusions Our study identifies a new autosomal disease, VKCFD1, caused by UPD. These data suggest that the Δ2GGCX isoform may retain enzymatic activity, and strongly encourage the evaluation of both hepatic and non-hepatic vitamin K-dependent proteins to assess differing responses to vitamin K supplementation in VKCFD patients.

[Nutrition iodine status in pregnant women in the sanitary district Sierra de Huelva-Andévalo, South of Spain]. / Deficiencia nutricional de yodo en gestantes pertenecientes al distrito sanitario Sierra de Huelva-Andévalo, sur de España.

BACKGROUND: Iodine is an essential trace element implicated in synthesis of thyroid hormones. Iodine requirements vary throughout life. This iodine requirement is increased during pregnancy and breastfeeding. In a previous study carried out by our group in 2008, we detected an iodine-deficient area in the province of Huelva, specially in district Sierra de Huelva-Andévalo by means of neonatal TSH determinations. OBJECTIVE: To reinforce the iodine supplementation campaign and its impact on their newborns in order to assess nutrition iodine status in pregnant women using questionnaire and ioduria determination. MATERIAL AND METHODS: This study has been jointly carried out by Congenital Hypothyroidism Unit of the Clinical Biochemistry Department of the Virgen Macarena University Hospital (Seville) and the Gynecology and Clinical Analysis Unit of the Río Tinto Hospital (Huelva) during two years. We studied 313 pregnant women. All of them filled out a personal questionnaire to know the iodine nutritional status in their area. Ioduria was determinated by high-resolution liquid chromatography. Data from pregnant women and results of the studied variables were analyzed with SPSS v13.0. CONCLUSIONS: Pregnant women from the sanitary district Sierra de Huelva-Andévalo present a median for ioduria which corresponds to an insufficient iodine intake according to the WHO classification. The questionnaires suggest that this iodine deficiency is consequence of an insufficient iodine intake and a low adherence to the treatment.