New mechanisms involved in paternal 20q disomy associated with pseudohypoparathyroidism.
OBJECTIVE
Type I pseudohypoparathyroidism (PHP-I) can be subclassified into Ia and Ib, depending on the presence or absence of Albright's hereditary osteodystrophy's phenotype, diminished α-subunit of the stimulatory G protein (G(s)α) activity and multihormonal resistance. Whereas PHP-Ia is mainly associated with heterozygous inactivating mutations in G(s)α-coding exons of GNAS, PHP-Ib is caused by imprinting defects of GNAS. To date, just one patient with PHP and complete paternal uniparental disomy (UPD) has been described. We sought to identify the underlining molecular defect in twenty patients with parathyroid hormone resistance, hypocalcemia and hyperphosphatemia, and abnormal methylation pattern at GNAS locus.


METHODS
Microsatellite typing and comparative genome hybridization were performed for proband and parents.


RESULTS
We describe four patients with partial paternal UPD of chromosome 20 involving pat20qUPD in one case, from 20q13.13-qter in two cases, and pat20p heterodisomy plus interstitial 20q isodisomy in one patient.


CONCLUSIONS
These observations demonstrate that mitotic recombination of chromosome 20 can also give rise to UPD and PHP, a situation similar to other imprinting disorders, such as Beckwith-Wiedemann syndrome or neonatal diabetes.
Fernández-Rebollo
Eduardo
E
Endocrinology and Diabetes Research Group, Molecular Genetics Laboratory, Hospital de Cruces, 48903 Barakaldo, Bizkaia, Spain.
Lecumberri
Beatriz
B
Garin
Intza
I
Arroyo
Javier
J
Bernal-Chico
Ana
A
Goñi
Fernando
F
Orduña
Rosa
R
Castaño
Luis
L
de Nanclares
Guiomar Pérez
GP
D000328:Adult; D002675:Child, Preschool; D002864:Chromogranins; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D008297:Male; D008745:Methylation; D018895:Microsatellite Repeats; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011547:Pseudohypoparathyroidism / Q000235:genetics*; D024182:Uniparental Disomy
D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs