Phenotypic analysis, dominant

Burren, C. P., Curley, A., Christie, P., Rodda, C. P., and Thakker, R. V. (2005) A family with autosomal dominant hypocalcaemia with hypercalciuria (ADHH) mutational analysis, phenotypic variability and treatment challenges. J. Pediatr. Endocrinol. Metab. 18, 9-99. 

Three disorders of lipoprotein metabolism share these characteristics familial hypobetal-ipoproteinemia, chylomicron retention disease, and ABL (Table 27-2). The presence or absence of specific plasma apoB lipoproteins, as well as their mode of inheritance, can be useful when attempting to differentiate between these disorders. Symptoms associated with familial hypo-betalipoproteinemia are usually milder than for the other two and are inherited as dominant traits, that is, symptoms are observed in at least one parent of an affected offspring. Chylomicron retention disease is an autosomal recessive disorder with a severe phenotype commonly presenting soon after birth. Plasma lipoprotein analysis from affected individuals shows a specific absence of chylomicrons (apoB48) but normal amounts of VLDL and LDL (apoB 100). In our patient, evidence of recessive inheritance and absence of all apoB-containing lipoproteins implicates ABL as the most likely diagnosis. 

Hypophosphatasia is caused by recessive mutations in the gene coding for tissue nonspecific alkaline phosphatase (TNSALP formerly liver/bone/kid-ney type alkaline phosphatase) on chromosome Ip [14,15]. The sensitivity and speed of mutation analysis has turned it into a valuable diagnostic tool. Over 50 different mutations have been identified. There are reasonably good genotype-phenotype correlations [16], probably explained by the type and site of the individual mutations and their structural consequences. Rarely, mild forms of the disease appear to be transmitted as dominant traits. In one such family, a TNSALP mutation was identified which upon coexpression in cultured cells reduced the activity of wild-type TNSALP [17]. 

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