Mutations in HPSE2 Cause Urofacial Syndrome

Daly, Sarah B.; Urquhart, Jill; Hilton, Emma; McKenzie, Edward A.; Kammerer, Richard A.; Lewis, Malcolm J.; Kerr, Bronwyn; Stuart, Helen M.; Long, David A.; Burgu, Berk; Aydoğdu, Özgü; Derbent, Murat; García‐Miñaúr, Sixto; Gener, Blanca; Shalev, Stavit A.; Smith, R. A.; Woolf, Adrian S.; Black, Graeme; Newman, William G.

doi:10.1016/j.ajhg.2010.07.010

Cited by 13 publications

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“…18 Patient B268 presented with isolated CAKUT and was found to harbor a previously reported truncating mutation in the gene HPSE2. 19 This gene is responsible for urofacial syndrome. 19,20 This syndrome, also known as Ochoa syndrome, is characterized by typical distorted facial expression with smiling or laughing expression as well as bladder malfunctions leading to voiding dysfunction, recurrent urinary tract infections, and other accompanying features of CAKUT.…”

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confidence: 99%

“…19 This gene is responsible for urofacial syndrome. 19,20 This syndrome, also known as Ochoa syndrome, is characterized by typical distorted facial expression with smiling or laughing expression as well as bladder malfunctions leading to voiding dysfunction, recurrent urinary tract infections, and other accompanying features of CAKUT. After establishment of the molecular genetic diagnosis, we contacted the primary nephrologist who originally recruited this patient at a very young age and asked him to look for the typical facial grimacing associated with this syndrome.…”

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confidence: 99%

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Exome Sequencing Discerns Syndromes in Patients from Consanguineous Families with Congenital Anomalies of the Kidneys and Urinary Tract

Vivante

Hwang

Kohl

et al. 2016

JASN

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Congenital anomalies of the kidneys and urinary tract (CAKUT) are the leading cause of CKD in children, featuring a broad variety of malformations. A monogenic cause can be detected in around 12% of patients. However, the morphologic clinical phenotype of CAKUT frequently does not indicate specific genes to be examined. To determine the likelihood of detecting causative recessive mutations by wholeexome sequencing (WES), we analyzed individuals with CAKUT from 33 different consanguineous families. Using homozygosity mapping and WES, we identified the causative mutations in nine of the 33 families studied (27%). We detected recessive mutations in nine known disease-causing genes: ZBTB24, WFS1, HPSE2, ATRX, ASPH, AGXT, AQP2, CTNS, and PKHD1. Notably, when mutated, these genes cause multiorgan syndromes that may include CAKUT as a feature (syndromic CAKUT) or cause renal diseases that may manifest as phenocopies of CAKUT. None of the above monogenic disease-causing genes were suspected on clinical grounds before this study. Follow-up clinical characterization of those patients allowed us to revise and detect relevant new clinical features in a more appropriate pathogenetic context. Thus, applying WES to the diagnostic approach in CAKUT provides opportunities for an accurate and early etiology-based diagnosis and improved clinical management.

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confidence: 99%

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confidence: 99%

Exome Sequencing Discerns Syndromes in Patients from Consanguineous Families with Congenital Anomalies of the Kidneys and Urinary Tract

Vivante

Hwang

Kohl

et al. 2016

JASN

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“…Both HPSE2 and LRIG2 transcripts were detected in nerve trunks invading the first trimester bladder (2,3,11). The exact biological function of HPSE2 and LRIG2 is not clear, but it was hypothesized that both proteins play a key role in the regulatory network of bladder function (11).…”

Section: Discussionmentioning

confidence: 99%

“…However, there are still some UFS families the members of which had none of these mutations. In addition, some family members with the same mutation may have no grimacing but BD or may have no BD but just characteristic grimacing while their siblings have full-blown UFS in some series (3,9).…”

Section: Discussionmentioning

confidence: 99%

Chronic Kidney Disease in a Boy with Enuresis: The Diagnosis Behind the Smile

Demir

Hall²,

Newman³

2017

Turk Neph Dial Transpl

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A 13-year-old boy was admitted with enuresis. He had no history of urinary tract infection, daytime incontinence or fecal incontinence. Previously performed ultrasound had revealed bilateral hydroureteronephrosis and trabeculated bladder. Voiding cystoureterography had detected multiple diverticuli without reflux. Renal scan had revealed reduced uptake with multiple renal scarring and diuretic renogram had shown bilateral obstruction. Urodynamic evaluation had revealed non-compliant hyperactive bladder and significant residual volume. Laboratory tests had been consistent with chronic kidney disease and he had been referred to our clinic. On admission, he was diagnosed with urofacial syndrome, due to the grimacing expression while trying to smile on physical examination, and the diagnosis was further confirmed by genetic analysis during follow-up. This case was reported to increase the awareness of physicians about this rare cause of chronic kidney disease as early diagnosis is mandatory. Asking the patient to smile would easily lead to the diagnosis.Key WORdS: Urofacial syndrome, Chronic kidney disease, Enuresis, Children ÖzOn üç yaşında erkek olgu geceleri idrar kaçırma şikayeti ile başvurdu. Geçirilmiş idrar yolu enfeksiyonu, gündüz idrar kaçırma ya da dışkı kaçırma gibi şikayetlerinin olmadığını belirtti. Başvuru öncesi yapılan ultrasonografisinde bilateral hidroüreteronefrozunun olduğu ve mesanesinin trabeküle olduğu görüldü. İşeme sistoüretrogramında reflüsünün olmadığı ancak çoklu divertiküllerinin olduğu gözlendi. Diüretik renogramında bilateral obstrüksiyonu izlendi. Ürodinamik değerlendirmede kompliyansı düşük hiperaktif mesanesinin olduğu ve anlamlı miktarda rezidüel idrarının kaldığı görüldü. Laboratuvar testlerinin kronik böbrek hastalığı ile uyumlu olması üzerine olgu kliniğimize yönlendirildi. Başvurusunda olgunun fizik bakısında gülmeye çalışırken yüzünde gelişen ağlama/buruşma ifadesi nedeni ile ürofasyal sendrom tanısı aldı ve izleminde tanısı genetik olarak doğrulandı. Olgu, erken tanının önemli olduğu son dönem böbrek yetmezliğinin nadir nedenlerinden olan ürofasyal sendrom konusunda hekimlerin farkındalığını arttırmak amacı ile sunulmuştur. Hastadan sadece gülümsemesini istemek kolaylıkla tanıya götürmektedir.aNaHtaR SÖzCüKleR: Ürofasyal sendrom, Böbrek yetmezliği, Enürezis, Çocuk

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“…87 Mutations affecting the gene HPSE2, which encodes the heparanase-2 enzyme, provide the genetic basis of uFs. 88,89 de lange syndrome Patients with de Lange syndrome have distinctive facial features, growth retardation, hirsutism, and upper limb reduction defects. 82 vur has been reported in 12% of patients with the disorder.…”

Section: N a T U R E R E V I E W S U N C O R R E C T E D P R O O Fmentioning

confidence: 99%

Genetics of vesicoureteral reflux

et al. 2011

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| Primary vesicoureteral reflux (VUR) is the most common urological anomaly in children, affecting 1-2% of the pediatric population and 30-40% of children presenting with urinary tract infections (UTIs). Refluxassociated nephropathy is a major cause of childhood hypertension and chronic renal failure. The hereditary and familial nature of VUR is well recognized and several studies have reported that siblings of children with VUR have a higher incidence of reflux than the general pediatric population. Familial clustering of VUR implies that genetic factors have an important role in its pathogenesis, but no single major locus or gene for VUR has yet been identified and most researchers now acknowledge that VUR is genetically heterogeneous. Improvements in genome-scan techniques and continuously increasing knowledge of the genetic basis of VUR should help us to further understand its pathogenesis.

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Mutations in HPSE2 Cause Urofacial Syndrome

Cited by 13 publications

References 0 publications

Exome Sequencing Discerns Syndromes in Patients from Consanguineous Families with Congenital Anomalies of the Kidneys and Urinary Tract

Exome Sequencing Discerns Syndromes in Patients from Consanguineous Families with Congenital Anomalies of the Kidneys and Urinary Tract

Chronic Kidney Disease in a Boy with Enuresis: The Diagnosis Behind the Smile

Genetics of vesicoureteral reflux

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