G2Cdb::Human Disease report

Disease id
D00000143
Name
Pseudohypoparathyroidism
Nervous system disease
no

Genes (1)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00001473 GNAS
GNAS complex locus
Y (9876352) Deletion (D) Y
G00001473 GNAS
GNAS complex locus
Y (9876352) Microinsertion (MI) Y
G00001473 GNAS
GNAS complex locus
Y (9876352) Microinsertion (MI) Y
G00001473 GNAS
GNAS complex locus
Y (16116826) Nonsense (No) Y

References

  • Albright's hereditary osteodystrophy (pseudohypoparathyroidism type Ia): clinical case with a novel mutation of GNAS1.

    Garavelli L, Pedori S, Zanacca C, Caselli G, Loiodice A, Mantovani G, Ammenti A, Virdis R and Banchini G

    Department of Pediatrics, S. Maria Nuova Hospital, Reggio Emilia, Italy. garavelli.livia@asmn.re.it

    Albright's hereditary osteodystrophy is characterized by ectopic calcification and ossification, round face, short hands and feet with short terminal phalanges, short metacarpals (especially 4th and 5th) and absence of the 4th knuckle (brachydactyly type E). Here we describe a case that recently came to our attention of a girl suffering from seizures caused by hypocalcaemia, in which the clinical diagnosis of Albright's hereditary osteodystrophy and Pseudohypoparathyroidism (PHP) (Pseudohypoparathyroidism Ia) was confirmed by DNA molecular analysis. This analysis revealed a novel mutation of GNAS 1, resulting in the nonsense mutation of exon 13 (CAG-->TAG, codon 384). This result expands the spectrum of GNAS1 mutations associated with this disorder.

    Acta bio-medica : Atenei Parmensis 2005;76;1;45-8

  • GNAS1 mutational analysis in pseudohypoparathyroidism.

    Ahmed SF, Dixon PH, Bonthron DT, Stirling HF, Barr DG, Kelnar CJ and Thakker RV

    MRC Molecular Endocrinology Group, Imperial College School of Medicine, Hammersmith Hospital London, UK.

    Objective: Mutations of the GNAS1 gene, which is located on chromosome 20q13.11 and encodes the alpha-subunit of the stimulatory GTP-binding protein, have been identified in patients with pseudohypoparathyroidism type Ia (PHPIa) and pseudopseudohypoparathyroidism (PPHP). We have undertaken studies to determine the prevalence of GNAS1 mutations and to explore methods for their more rapid detection.

    Methods: Thirteen unrelated families (8 with PHPIa and PPHP patients, and 5 with PPHP patients only) were investigated for GNAS1 mutations in the 1050 base-pair (bp) region spanning exons 2-13 by single-stranded conformational polymorphism (SSCP) and DNA sequence analysis.

    Results: GNAS1 mutations were detected in 4 of the 8 families with PHPIa patients. These consisted of: two novel de novo missense mutations (Pro115Ser and Glu259Val) in two families and an identical 4 bp deletion of codons 189 and 190 resulting in a frame-shift in two unrelated families. These results expand the spectrum of GNAS1 mutations associated with this disorder and confirm the presence of a mutational hot-spot involving codons 189 and 190. SSCP analysis was found to be a specific and sensitive method that detected all 4 mutations. GNAS1 mutations were not detected in any of the PPHP only families.

    Conclusions: The pseudohypoparathyroid disorders appear to represent a heterogeneous group with GNAS1 mutations forming the molecular aetiology in approximately 50% of pseudohypoparathyroidism type Ia families. Such mutations can be reliably identified by single-stranded conformational polymorphism and this will help to supplement the clinical evaluation of some patients and their families, particularly as the disease may not be fully penetrant.

    Clinical endocrinology 1998;49;4;525-31

Literature (2)

Pubmed - human_disease

  • Albright's hereditary osteodystrophy (pseudohypoparathyroidism type Ia): clinical case with a novel mutation of GNAS1.

    Garavelli L, Pedori S, Zanacca C, Caselli G, Loiodice A, Mantovani G, Ammenti A, Virdis R and Banchini G

    Department of Pediatrics, S. Maria Nuova Hospital, Reggio Emilia, Italy. garavelli.livia@asmn.re.it

    Albright's hereditary osteodystrophy is characterized by ectopic calcification and ossification, round face, short hands and feet with short terminal phalanges, short metacarpals (especially 4th and 5th) and absence of the 4th knuckle (brachydactyly type E). Here we describe a case that recently came to our attention of a girl suffering from seizures caused by hypocalcaemia, in which the clinical diagnosis of Albright's hereditary osteodystrophy and Pseudohypoparathyroidism (PHP) (Pseudohypoparathyroidism Ia) was confirmed by DNA molecular analysis. This analysis revealed a novel mutation of GNAS 1, resulting in the nonsense mutation of exon 13 (CAG-->TAG, codon 384). This result expands the spectrum of GNAS1 mutations associated with this disorder.

    Acta bio-medica : Atenei Parmensis 2005;76;1;45-8

Pubmed - other

  • GNAS1 mutational analysis in pseudohypoparathyroidism.

    Ahmed SF, Dixon PH, Bonthron DT, Stirling HF, Barr DG, Kelnar CJ and Thakker RV

    MRC Molecular Endocrinology Group, Imperial College School of Medicine, Hammersmith Hospital London, UK.

    Objective: Mutations of the GNAS1 gene, which is located on chromosome 20q13.11 and encodes the alpha-subunit of the stimulatory GTP-binding protein, have been identified in patients with pseudohypoparathyroidism type Ia (PHPIa) and pseudopseudohypoparathyroidism (PPHP). We have undertaken studies to determine the prevalence of GNAS1 mutations and to explore methods for their more rapid detection.

    Methods: Thirteen unrelated families (8 with PHPIa and PPHP patients, and 5 with PPHP patients only) were investigated for GNAS1 mutations in the 1050 base-pair (bp) region spanning exons 2-13 by single-stranded conformational polymorphism (SSCP) and DNA sequence analysis.

    Results: GNAS1 mutations were detected in 4 of the 8 families with PHPIa patients. These consisted of: two novel de novo missense mutations (Pro115Ser and Glu259Val) in two families and an identical 4 bp deletion of codons 189 and 190 resulting in a frame-shift in two unrelated families. These results expand the spectrum of GNAS1 mutations associated with this disorder and confirm the presence of a mutational hot-spot involving codons 189 and 190. SSCP analysis was found to be a specific and sensitive method that detected all 4 mutations. GNAS1 mutations were not detected in any of the PPHP only families.

    Conclusions: The pseudohypoparathyroid disorders appear to represent a heterogeneous group with GNAS1 mutations forming the molecular aetiology in approximately 50% of pseudohypoparathyroidism type Ia families. Such mutations can be reliably identified by single-stranded conformational polymorphism and this will help to supplement the clinical evaluation of some patients and their families, particularly as the disease may not be fully penetrant.

    Clinical endocrinology 1998;49;4;525-31

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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