Familial Albright`s hereditary osteodystrophy with hypoparathyroidism: Normal structural G{sub s}{alpha} gene

Journal Article · Mon Apr 01 04:00:00 EST 1996 · Journal of Clinical Endocrinology and Metabolism

DOI:https://doi.org/10.1210/jc.81.4.1660· OSTI ID:530769

Shapira, H; Friedman, E; Farfel, Z ^[1]

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1. Tel Aviv Univ. (Israel); and others

Albright`s hereditary osteodystrophy (AHO) is a characteristic skeletal phenotype, including short stature, obesity, round face, and brachydactyly. AHO appears in patients with pseudohypoparathyroidism (PHP) who have resistance to PTH and in their eumetabolic family members who have pseudohypoparathyroidism (PPHP). The differential diagnosis of AHO in families without PHP includes brachydactyly E, whose existence as a distinct entity has been questioned. We studied a patient with familial AHO who presented with hypocalcemia. To our surprise, PTH levels were low, and the response to PTH administration was normal. This is the first case of familial AHO with hypoparathyroidism. The proband`s family included 22 affected subjects spanning 3 generations, who had variable degrees of AHO manifestations, with an autosomal dominant inheritance trait. The metacarpophalangeal pattern profile was typical of that of PHP-PPHP. As deficient activity and inactivating mutations of G{sub s}{alpha} were described in PHP as well as in PPHP, we measured the biological activity of G{sub s} in family members, which was normal. To exclude subtle abnormalities in the G{sub s}{alpha} gene, we sequenced the entire coding region of G{alpha} in the propositus, which was normal. We conclude that hypocalcemia should be adequately evaluated even in the presence of familial AHO, and that familial AHO can occur with a normal coding structural Ga gene. Identification of the molecular defect in familial AHO without PHP will shed light on the pathogenesis of AHO in general. 20 refs., 3 figs.

• OSTI ID: 530769
• Journal Information: Journal of Clinical Endocrinology and Metabolism, Journal Name: Journal of Clinical Endocrinology and Metabolism Journal Issue: 4 Vol. 81; ISSN JCEMAZ; ISSN 0021-972X
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
DIAGNOSIS
DNA SEQUENCING
DNA-CLONING
GENE MUTATIONS
GENES
GENETICS
HEREDITARY DISEASES
METABOLIC DISEASES
PATHOGENESIS
PATIENTS
PHENOTYPE
POLYMERASE CHAIN REACTION
SKELETAL DISEASES
STRUCTURE-ACTIVITY RELATIONSHIPS