A phenocopy of CAII deficiency: a novel genetic explanation for inherited infantile osteopetrosis with distal renal tubular acidosis

Borthwick, Katherine

doi:10.1136/jmg.40.2.115

Cited by 99 publications

(63 citation statements)

References 23 publications

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“…Previous studies showed that early SNHL (before the age of 10 yr) occurred in 37 of 40 patients with mutations in the ATP6V1B1 gene and that late-onset SNHL (between the ages of 10 and 40 yr) was observed in patients with ATP6V0A4 gene mutations (5)(6)(7)9,10). In our group, seven of Figure 1.…”

Section: Discussionsupporting

confidence: 53%

Genetic Investigation of Autosomal Recessive Distal Renal Tubular Acidosis

Vargas‐Poussou

Houillier²,

Pottier³

et al. 2006

Journal of the American Society of Nephrology

118

109

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Mutations in the ATP6V1B1 and ATP6V0A4 genes, encoding subunits B1 and 4 of apical H ؉ ATPase, cause recessive forms of distal renal tubular acidosis (dRTA). ATP6V1B mutations have been associated with early sensorineural hearing loss (SNHL), whereas ATP6V0A4 mutations are classically associated with either late-onset SNHL or normal hearing. The phenotype and genotype of 39 new kindreds with recessive dRTA, 18 of whom were consanguineous, were assessed. Novel and known loss-of-function mutations were identified in 31 kindreds. Fourteen new and five recurrent mutations of the ATP6V0A4 gene were identified in 21 families. For the ATP6V1B1 gene, two new and two previously described mutations were identified in 10 families. Surprisingly, seven probands with ATP6V0A4 gene mutations developed severe early SNHL between the ages of 2 mo and 10 yr. No mutation was detected in eight families. These data extend the spectrum of disease-causing mutations and provide evidence for genetic heterogeneity in SNHL. The data also demonstrate that mutations in either of these genes may cause early deafness, and they highlight the importance of genetic screening for recessive forms of dRTA independent of hearing status.

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Section: Discussionsupporting

confidence: 53%

Genetic Investigation of Autosomal Recessive Distal Renal Tubular Acidosis

Vargas‐Poussou

Houillier²,

Pottier³

et al. 2006

Journal of the American Society of Nephrology

118

109

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“…CA2 in osteoclast plays an important role in bone resorption. Deficiency of CA2 can cause inherited infantile osteopetrosis with distal renal tubular acidosis in human (Borthwick et al, 2003). Gay et al (1985) found that activity of CA2 was diminished in the proximal part of the lesion and was zero in the distal lesion.…”

Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed genes in the growth plate of broiler chickens with thiram-induced tibial dyschondroplasia

Tian

Zhang

et al. 2009

Avian Pathology

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Tibial dyschondroplasia (TD) is characterized by expansion of the proximal growth plates of the tibiotarsus that fail to form bone, lack blood vessels, and contain non-viable cells. Thiram (a carbamate pesticide), when fed to young broiler chicks, induces TD with high regularity and precision. We used this experimental model to understand the cause of the defects associated with TD by selecting and identifying the genes differentially expressed in the TD growth plate of broiler chickens. Broiler chicks at 7 days of age were randomly divided into two groups. After fasting overnight, they were fed with regular diet (control) or the same diet containing 100 mg/kg thiram for 96 h to induce TD (thiram-fed). mRNA was purified from the growth plates of control and thiram-fed broilers. Forward and reverse-subtracted cDNA libraries were generated by suppression subtractive hybridization technology. Ten selected genes from cDNA libraries were identified by real-time quantitative polymerase chain reaction. All were differentially expressed in TD growth plates (PB0.05 or PB0.01). The levels of collagen type X (Col X), pro-alpha-1 collagen type I (Col I a1), collagen type IX (Col IX), NADH dehydrogenase (NADH DH), cytochrome C oxidase subunit III (COX III), enolase 1, alpha (ENO1), carbonic anhydrase II (CA2) and heat shock protein 90 (Hsp90) mRNA transcripts were upregulated, while the expression levels of Matrilin 3 (MATN3) and chondromodulin-I (ChM-I) were downregulated. Col I and Hsp90 were detected by immunohistochemistry at different stages. Given that these genes are involved in matrix formation, endochondral ossification, developmental regulation, electron transport in the mitochondrial respiratory chain and vascularization, our findings may provide new insights into understanding the pathogenesis of TD.

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“…Secondly, MEN1 phenocopy is more likely to involve parathyroid and anterior pituitary tumours rather than pancreatic neuroendocrine tumours, and these coincidental occurrences are likely explained by the commoner occurrence of parathyroid and pituitary tumours in the population, which occur with incidences of up to 28 per 100,000 per year and 0.4-8 per 100,000 per year, respectively, rather than pancreatic neuroendocrine tumours which occur with an incidence of only one per million per year [Monson, 2000;Ciccarelli et al, 2005]. The occurrence of phenocopies is not confined to MEN1, but has also been reported to occur in Huntington's disease [Moore et al, 2001], breast cancer, in the context of hereditary non polyposis colorectal cancer [Caluseriu et al, 2001], and infantile osteopetrosis with distal renal tubular acidosis [Borthwick et al, 2003]. Thus, it would seem that phenocopy occurrence is likely to occur in other hereditary disorders, and its recognition is therefore of importance in providing a correct diagnosis and for optimal clinical management of the patients and their families.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic challenges due to phenocopies: lessons from Multiple Endocrine Neoplasia type1 (MEN1)

et al. 2010

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Phenocopies may confound the clinical diagnoses of hereditary disorders. We report phenocopies in Multiple Endocrine Neoplasia type 1 (MEN1), an autosomal dominant disorder, characterised by the combined occurrence of parathyroid, pituitary and pancreatic tumours. We studied 261 affected individuals from 74 families referred with a clinical diagnosis of MEN1 and sought inconsistencies between the mutational and clinical data. We identified four patients from unrelated families with phenocopies. Patients 1 and 2 from families with MEN1, developed prolactinomas as the sole endocrinopathy but they did not harbour the germline MEN1 mutation present in their affected relatives. Patient 3, had acromegaly and recurrent hypercalcaemia following parathyroidectomy, whilst patient 4 had parathyroid tumours and a microprolactinoma. Patients 3 and 4 and their relatives did not have MEN1 mutations, but instead had familial hypocalciuric hypercalcaemia (FHH) due to a calcium-sensing receptor mutation (p.Arg680Cys), and the hyperparathyroidism-jaw tumour (HPT-JT) syndrome due to a hyperparathyroidism type 2 deletional-frameshift mutation (c.1239delA), respectively. Phenocopies may mimic MEN1 either by occurrence of a single sporadic endocrine tumour in a patient with familial MEN1, or occurrence of two endocrine abnormalities associated with different aetiologies. Phenocopies arose in >5% of MEN1 families, and awareness of them is important in the clinical management of MEN1 and other hereditary disorders.

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A phenocopy of CAII deficiency: a novel genetic explanation for inherited infantile osteopetrosis with distal renal tubular acidosis

Cited by 99 publications

References 23 publications

Genetic Investigation of Autosomal Recessive Distal Renal Tubular Acidosis

Genetic Investigation of Autosomal Recessive Distal Renal Tubular Acidosis

Identification of differentially expressed genes in the growth plate of broiler chickens with thiram-induced tibial dyschondroplasia

Diagnostic challenges due to phenocopies: lessons from Multiple Endocrine Neoplasia type1 (MEN1)

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