Familial hypomagnesemia maps to chromosome 9q, not to the X chromosome: genetic linkage mapping and analysis of a balanced translocation breakpoint

Familial hypomagnesemia with secondary hypocalcemia (HSH) (MIM 307600) was studied in three inbred Bedouin kindreds from Israel. The three kindreds, one extended and two nuclear families, contained 13 affected individuals, 11 males and two females. Assuming that the individuals affected with hypomagnesemia shared a chromosomal region inherited from a common ancestor, we used a DNA pooling strategy in a genome-wide search for loci which show homozygosity for shared alleles in affected individuals. DNA samples from affected individuals within a single kindred were pooled and used as the template for PCR amplification of short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected siblings and parents were used as controls. A shift towards homozygosity was observed in the affected DNA pool compared with the control pools with D9S301 (GATA7D12). Genotyping of individual DNA samples with D9S301 and several flanking markers confirmed linkage to chromosome 9 with maximum LOD scores of 3.4 (theta = 0.05), 3.7 (theta = 0) and 2.3 (theta = 0) for the three families. We have identified a 14 cM interval on chromosome 9 (9q12-9q22.2), flanked by proximal marker D9S1874 and distal marker D9S1807, within which all affected individuals from the three kindreds are homozygous for a shared haplotype. The disease segregates with a common affected haplotype in the three families, suggesting that hypomagnesemia is caused by a common ancestral mutation in these families. Although HSH has been previously reported to be X linked, these linkage data demonstrate that the disorder is an autosomal recessive disease in these kindreds. Mapping of a chromosomal breakpoint in a somatic cell line established from a patient with HSH and a balanced X;9 translocation placed the chromosomal breakpoint in a 500 kb region flanked by D9S1844 and D9S273. Identification of the gene responsible for hypomagnesemia will provide insight into the regulation of this essential cation.      

New Danish reference values for height,weight and body mass index of children aged 0–5 years

Aim: To derive new reference values for height, weight and body mass index (BMI) of children aged 0–5 years in Denmark and to compare them with the national reference from the 1970s and the 2006 WHO standard. Methods: The height and weight of 4105 healthy singleton children born in 1995 were obtained from a cohort study. Children were measured at birth and at seven regular health examinations by a general practitioner up to 5 years of age. Generalized additive models for location, scale and shape were used to construct percentile curves. Results: Mean length, weight and BMI at birth and during the first months of life increased significantly, but the differences diminished thereafter, and at 1 year BMI had decreased. In boys, weight and BMI had decreased by 2 years of age but had increased, together with height, at 5 years. Children were taller, heavier and had a higher BMI than that referred to in the WHO standard. Conclusion: New references for length or height, weight and BMI by age were constructed for children in Denmark. Since the 1970s, weight, length and BMI at birth increased, and growth during the first year of life appears to be healthier.