Loss-of-Function Mutations in HPSE2 Cause the Autosomal Recessive Urofacial Syndrome

Pang, Junfeng; Zhang, Shu; Yang, Ping; Hawkins-Lee, Bobbilynn; Zhong, Jixin; Zhang, Yushan; Ochoa, Bernardo; Agúndez, José A.G.; Voelckel, Marie‐Antoinette; Fisher, Richard; Gu, Weikuan; Xiong, Wen-Cheng; Mei, Lin; She, Jin‐Xiong; Wang, Cong Yi

doi:10.1016/j.ajhg.2010.04.016

Cited by 83 publications

(62 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Homozygosity-mapping, on the other hand, is a more powerful and effective approach to study recessive disorders in consanguineous families (Harville et al 2010;Pang et al 2010;Iseri et al 2010;Collin et al 2010). For those disorders that are not amendable to these two conventional approaches, their causal variants remain elusive.…”

Section: Introductionmentioning

confidence: 97%

Revisiting Mendelian disorders through exome sequencing

2011

View full text Add to dashboard Cite

Over the past several years, more focus has been placed on dissecting the genetic basis of complex diseases and traits through genome-wide association studies. In contrast, Mendelian disorders have received little attention mainly due to the lack of newer and more powerful methods to study these disorders. Linkage studies have previously been the main tool to elucidate the genetics of Mendelian disorders; however, extremely rare disorders or sporadic cases caused by de novo variants are not amendable to this study design. Exome sequencing has now become technically feasible and more cost-effective due to the recent advances in high-throughput sequence capture methods and next-generation sequencing technologies which have offered new opportunities for Mendelian disorder research. Exome sequencing has been swiftly applied to the discovery of new causal variants and candidate genes for a number of Mendelian disorders such as Kabuki syndrome, Miller syndrome and Fowler syndrome. In addition, de novo variants were also identified for sporadic cases, which would have not been possible without exome sequencing. Although exome sequencing has been proven to be a promising approach to study Mendelian disorders, several shortcomings of this method must be noted, such as the inability to capture regulatory or evolutionary conserved sequences in non-coding regions and the incomplete capturing of all exons.

show abstract

Section: Introductionmentioning

confidence: 97%

Revisiting Mendelian disorders through exome sequencing

2011

View full text Add to dashboard Cite

show abstract

“…This approach has been shown to be powerful and is particularly useful in investigating autosomal recessive disorders especially in populations with a high prevalence of consanguinity. This is evident from the enormous number of studies identifying causal mutations for autosomal recessive disorders in consanguineous families (Abu SaWeh et al 2010;Harville et al 2010;Walsh et al 2010;Pang et al 2010;Lapunzina et al 2010;Nicolas et al 2010;Uz et al 2010;Iseri et al 2010;Collin et al 2010). However, the Wrst study applying the homozygosity association approach at the genome-wide scale for complex diseases only appeared in 2007 (Lencz et al 2007).…”

Section: Implications On Complex Diseases and Traitsmentioning

confidence: 94%

Regions of homozygosity and their impact on complex diseases and traits

Naidoo

Teo

et al. 2010

Hum Genet

View full text Add to dashboard Cite

Regions of homozygosity (ROHs) are more abundant in the human genome than previously thought. These regions are without heterozygosity, i.e. all the genetic variations within the regions have two identical alleles. At present there are no standardized criteria for defining the ROHs resulting in the different studies using their own criteria in the analysis of homozygosity. Compared to the era of genotyping microsatellite markers, the advent of high-density single nucleotide polymorphism genotyping arrays has provided an unparalleled opportunity to comprehensively detect these regions in the whole genome in different populations. Several studies have identified ROHs which were associated with complex phenotypes such as schizophrenia, late-onset of Alzheimer's disease and height. Collectively, these studies have conclusively shown the abundance of ROHs larger than 1 Mb in outbred populations. The homozygosity association approach holds great promise in identifying genetic susceptibility loci harboring recessive variants for complex diseases and traits.

show abstract

“…However, UFS-causing gene mutations were first reported by two groups in 2010 [13,14]. To date, 10 different HPSE2 gene mutations have been reported in a total of 28 UFS patients from 17 families in different studies [13,14,15,16].…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies showed that HPSE2 and LRIG2 mutations have not been detected in all patients. Pang et al [14] evaluated nine families with UFS and have detected HPSE2 mutations in all families. However, Daly et al [13] found HPSE2 mutations in six (60%) of 10 families.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, biallelic mutations of HPSE2 (chromosome 10q24.2) (MIM 236730) and LRIG2 (chromosome 1p13.2) (MIM 615112) have been reported in UFS patients [13,14,15,16,17]. Non-neurogenic neurogenic bladder (NNNB) also called Hinman-Allen syndrome has a bladder identical to that seen with UFS without typical facial features, for which the pathogenesis is unknown.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

<b><i>HPSE2</i></b> Mutations in Urofacial Syndrome, Non-Neurogenic Neurogenic Bladder and Lower Urinary Tract Dysfunction

Bulum

Özçakar

Duman

et al. 2015

Nephron

View full text Add to dashboard Cite

Background: Urofacial syndrome (UFS) is characterised by congenital bladder dysfunction accompanied by a characteristic abnormal grimace upon smiling and crying. In recent years, biallelic mutations of HPSE2 and LRIG2 have been reported in UFS patients. Non-neurogenic neurogenic bladder (NNNB) has a bladder identical to UFS without typical facial features. The aim of this study was to analyse HPSE2 mutations in patients with UFS and NNNB or severe lower urinary tract dysfunction (LUTD) without abnormal facial expression. Methods: Patients with UFS, NNNB and severe LUTD were enrolled in the study. We examined a total of 35 patients from 33 families. There were seven UFS patients from five different families, 21 patients with NNNB and seven with LUTD. HPSE2 gene mutation analysis was performed using the polymerase chain reaction protocol followed by Sanger sequencing in these patients. Results: A twin pair with UFS was found to be homozygous for c.457C>T (p.Arg153*) mutation. No other pathogenetic variant was detected. Conclusion:HPSE2 mutations were found in one UFS family but not detected in patients with NNNB and severe LUTD. Considering the increasingly recognised cases of NNNB that were diagnosed in early childhood period, genetic factors appear to be responsible. Thus, further genetic studies are needed to discover novel associated gene variants in these bladder anomalies.

show abstract

Loss-of-Function Mutations in HPSE2 Cause the Autosomal Recessive Urofacial Syndrome

Cited by 83 publications

References 21 publications

Revisiting Mendelian disorders through exome sequencing

Revisiting Mendelian disorders through exome sequencing

Regions of homozygosity and their impact on complex diseases and traits

<b><i>HPSE2</i></b> Mutations in Urofacial Syndrome, Non-Neurogenic Neurogenic Bladder and Lower Urinary Tract Dysfunction

Contact Info

Product

Resources

About