A novel GNAS mutation in an infant boy with pseudohypoparathyroidism type Ia and normal serum calcium and phosphate levels

Reis, Mariana Tenorio Antunes; Cattani, Andreina; Mendonca, Berenice B.; Corrêa, Pedro Henrique Silveira; Martin, Regina Matsunaga

doi:10.1590/s0004-27302010000800011

Cited by 4 publications

(3 citation statements)

References 9 publications

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“…There is some evidence to suggest that the Gs alpha mutation is paternally transmitted in patients with PPHP and maternally transmitted in patients with PHP-Ia. The gene may be imprinted in a tissue-specific manner6,8,9).…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel mutation in a patient with pseudohypoparathyroidism type Ia

Lee

Kim

et al. 2014

Korean J Pediatr

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Pseudohypoparathyroidism type Ia (PHP Ia) is a disorder characterized by multiform hormonal resistance including parathyroid hormone (PTH) resistance and Albright hereditary osteodystrophy (AHO). It is caused by heterozygous inactivating mutations within the Gs alpha-encoding GNAS exons. A 9-year-old boy presented with clinical and laboratory abnormalities including hypocalcemia, hyperphosphatemia, PTH resistance, multihormone resistance and AHO (round face, short stature, obesity, brachydactyly and osteoma cutis) which were typical of PHP Ia. He had a history of repeated convulsive episodes that started from the age of 2 months. A cranial computed tomography scan showed bilateral calcifications in the basal ganglia and his intelligence quotient testing indicated mild mental retardation. Family history revealed that the patient's maternal relatives, including his grandmother and 2 of his mother's siblings, had features suggestive of AHO. Sequencing of the GNAS gene of the patient identified a heterozygous nonsense mutation within exon 11 (c.637 C>T). The C>T transversion results in an amino acid substitution from Gln to stop codon at codon 213 (p.Gln213*). To our knowledge, this is a novel mutation in GNAS.

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Section: Discussionmentioning

confidence: 99%

Identification of a novel mutation in a patient with pseudohypoparathyroidism type Ia

Lee

Kim

et al. 2014

Korean J Pediatr

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“…The patient had normal serum concentrations of calcium and phosphate for his age, and just his elevated levels of TSH and his mother’s background was compatible with the diagnosis of PHP-Ia [17]. Mariana Tenorio Antunes Reis et al [20] have also reported an infant boy with AHO phenotype, normal calcium and phosphate levels, whose mother was diagnosed as PHP-Ia. The functional analysis of GNAS exons showed a novel heterozygous missense mutation in exon 5 of GNAS.…”

Section: Discussionmentioning

confidence: 99%

A patient with features of albright hereditory osteodystrophy and unusual neuropsychiatric findings without coding Gsalpha mutations

Hasani‐Ranjbar

Jouyandeh

Amoli

et al. 2014

J Diabetes Metab Disord

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BackgroundPseudohypoparathyroidism(PHP) is a heterogeneous group of rare metabolic disorders characterized by hypocalcemia and hyperphosphatemia resulting from PTH resistance. Different forms of PHP have been reported based on biochemical and clinical manifestation and genetic findings. Most of these forms are caused by defects in GNAS, an imprinted gene locus with multiple subunits. We reported a 12- year- old girl with unusual clinical manifestations of Pseudopseudohypoparathyroidism(PPHP).MethodsAfter clinical and biochemical evaluations, the patients’ genomic DNA was isolated from peripheral blood leukocytes using salting out method. The whole coding sequences of GNAS gene including 13 exons were amplified by PCR. Quantitative PCR reactions were performed too.FindingsWe described a 12- year- old girl with Albright Hereditory osteodystrophy (AHO) phenotype, poor school performance, some abnormal movements, TSH resistance with normal serum calcium and phosphorus levels and normal Gsα bioactivity with no mutation in GNAS exons. Unusual neuropsychiatric findings in this patient were compatible with Asperger syndrome.ConclusionsAccording to our findings this patient could not be categorized in any of PHP subgroups. Identifying of such individuals may be useful to discover different genetic patterns in pseudohypoparathyroidism and pseudopseudohypoparathyroidism. It is important to identify patients in whom PHP is caused by novel GNAS mutations, as careful investigations of these findings will likely further our knowledge of this complex and this unique disorder. In addition this case presented with unusual neuropsychiatric findings which has not been reported up to now.

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“…The GNAS gene is located on the long arm of chromosome 20 in the region 13.1 -13.2 and contains 13 exons. The inactivating mutations have been detected in all exons, with 20 % of the mutations occurring in exon 7 (2,3) .…”

Section: Introductionmentioning

confidence: 99%

Pseudohypoparathyroidism type Ia: a novel GNAS mutation in a Brazilian boy presenting with an early primary hypothyroidism

Alves

Sampaio

Barbieri

et al. 2013

Journal of Pediatric Endocrinology and Metabolism

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Pseudohypoparathyroidism type Ia (PHP Ia) is a rare disease characterized by an elevated parathyroid hormone due to the resistance to its action in target tissues. We report a new GNAS mutation causing PHP Ia and an atypical early-onset primary hypothyroidism. A 3-year-old boy was diagnosed with obesity, delayed pyschomotor development, and round face. The laboratory evaluation at the age of 1 year showed primary hypothyroidism, hypocalcemia, hyperphosphatemia, elevated alkaline phosphatase, and parathyroid hormone. These data led to the diagnosis of PHP Ia. Molecular analysis revealed a novel missense mutation in GNAS exon 1 (TCG→CGC, Cys3→Arg) in both the child and his mother. Although previously reported cases described delayed subclinical hypothyroidism as the more common thyroid abnormality, we report a not previously described GNAS mutation associated with an atypical early-onset primary hypothyroidism. These observations broaden the clinical spectrum of PHP Ia and its associated mutations.

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A novel GNAS mutation in an infant boy with pseudohypoparathyroidism type Ia and normal serum calcium and phosphate levels

Cited by 4 publications

References 9 publications

Identification of a novel mutation in a patient with pseudohypoparathyroidism type Ia

Identification of a novel mutation in a patient with pseudohypoparathyroidism type Ia

A patient with features of albright hereditory osteodystrophy and unusual neuropsychiatric findings without coding Gsalpha mutations

Pseudohypoparathyroidism type Ia: a novel GNAS mutation in a Brazilian boy presenting with an early primary hypothyroidism

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