Identification of a second kindred with familial hypocalciuric hypercalcemia type 3 (FHH3) narrows localization to a <3.5 megabase pair region on chromosome 19q13.3.

[familial hypocalciuric hypercalcemia]

Familial hypocalciuric hypercalcemia (FHH ) is a genetically heterogenous disorder that consists of three defined types , FHH 1 , FHH 2 , and FHH 3 whose chromosomal locations are 3 q 21 .1 , 19 p , and 19 q 13 , respectively . FHH 1 , caused by mutations of the calcium-sensing receptor (CASR ), occurs in more than 65 % of patients , whereas the abnormalities underlying FHH 2 and FHH 3 , which have each been described in single North American kindreds , are unknown .The aim of this study was to determine the basis of FHH in a proband , who did not have CASR mutations , and her kindred .The proband was a 43 -yr -old woman who presented with a corrected serum calcium of 2 .74 mmol /liter (normal = 2 .15 -2 .55 mmol /liter ), a serum PTH of 47 pg /ml (normal = 10 -65 pg /ml ), and a urinary calcium clearance :creatinine clearance of 0 .006 . She did not have a CASR mutation within the coding region and splice sites , and 24 members from three generations of her kindred were ascertained and investigated for serum abnormalities and cosegregation with polymorphic loci from chromosomes 3 q 21 .1 and 19 q 13 using leukocyte DNA .Sixteen members were hypercalcemic with normal or elevated serum PTH concentrations and mild hypophosphatemia , features consistent with FHH 3 . Use of microsatellite and single nucleotide polymorphic loci from chromosome 19 q 13 .3 demonstrated cosegregation with FHH in the kindred , with a peak LOD score = 5 .98 at 0 % recombination with D 19 S 412 . Analysis of recombinants mapped FHH to a 3 .46 -Mbp interval flanked centromerically by single nucleotide polymorphism rs 1990932 and telomerically by D 19 S 604 .FHH 3 may explain the calcium homeostasis disorder in those FHH patients who do not have CASR mutations .

Diseases
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Diseases presenting "mutations of the calcium-sensing receptor" symptom

familial hypocalciuric hypercalcemia

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