Paternal mosaicism and hereditary angioedema in a Taiwanese family

Yu, Tai-Chang; Shyur, Shyh-Dar; Huang, Li-Hsin; Wen, Da-Chin; Li, Jia-Shiuan

doi:10.1016/s1081-1206(10)60557-1

Cited by 6 publications

(4 citation statements)

References 11 publications

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“…pattern with high penetrance, and most patients are heterozygous 17 , although several cases of homozygosis [18][19][20][21][22] and two cases of gonadal mosaicism have been described 23,24 . Heterozygous patients have C1-INH plasma levels within 5-30% of normal values, rather than the 50% that might be expected.…”

Section: C1-inh-hae Has An Autosomal Dominant Inheritancementioning

confidence: 99%

The genetics of hereditary angioedema: A review

Piñero-Saavedra¹,

González-Quevedo²

2017

J Rare Dis Res Treat

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Section: C1-inh-hae Has An Autosomal Dominant Inheritancementioning

confidence: 99%

The genetics of hereditary angioedema: A review

Piñero-Saavedra¹,

González-Quevedo²

2017

J Rare Dis Res Treat

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“…The medical records of 215 patients from 183 unrelated families were collected, including the previous reports Chang and Hsu 2010;Chiang et al 2006;Chien et al 2004;Hung et al 1999Hung et al , 2001Lin et al 2005aLin et al , 2002bMa et al 2009;Wang et al 2004;Wen et al 2007;Weng and Shyur 2004;Yu et al 2007). The average incidence in a previous study from northern Taiwan covering a 20-year period was around 2.17 per 100,000 newborns .…”

Section: Distribution Patternsmentioning

confidence: 99%

Distribution, clinical features and treatment in Taiwanese patients with symptomatic primary immunodeficiency diseases (PIDs) in a nationwide population-based study during 1985–2010

Lee¹,

Huang²,

Jaing³

et al. 2011

Immunobiology

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“…Family 1. A c.[69_139=/del] has been shown in a family where three sons, but not the parents, show clinical and laboratory findings typical of HAE, with demonstrated allele segregation ( 99 ). c.69_139del variant has not been detected in DNA derived from somatic cells from the father and the mother, whereas it has occurred on the paternal transmitted chromosome.…”

Section: Inheritance Of Variantsmentioning

confidence: 99%

SERPING1 Variants and C1-INH Biological Function: A Close Relationship With C1-INH-HAE

Drouet

López‐Lera

Ghannam³

et al. 2022

Front. Allergy

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Hereditary angioedema with C1 Inhibitor deficiency (C1-INH-HAE) is caused by a constellation of variants of the SERPING1 gene (n = 809; 1,494 pedigrees), accounting for 86.8% of HAE families, showing a pronounced mutagenic liability of SERPING1 and pertaining to 5.6% de novo variants. C1-INH is the major control serpin of the kallikrein–kinin system (KKS). In addition, C1-INH controls complement C1 and plasminogen activation, both systems contributing to inflammation. Recognizing the failed control of C1s protease or KKS provides the diagnosis of C1-INH-HAE. SERPING1 variants usually behave in an autosomal-dominant character with an incomplete penetrance and a low prevalence. A great majority of variants (809/893; 90.5%) that were introduced into online database have been considered as pathogenic/likely pathogenic. Haploinsufficiency is a common feature in C1-INH-HAE where a dominant-negative variant product impacts the wild-type allele and renders it inactive. Small (36.2%) and large (8.3%) deletions/duplications are common, with exon 4 as the most affected one. Point substitutions with missense variants (32.2%) are of interest for the serpin structure–function relationship. Canonical splice sites can be affected by variants within introns and exons also (14.3%). For noncanonical sequences, exon skipping has been confirmed by splicing analyses of patients' blood-derived RNAs (n = 25). Exonic variants (n = 6) can affect exon splicing. Rare deep-intron variants (n = 6), putatively acting as pseudo-exon activating mutations, have been characterized as pathogenic. Some variants have been characterized as benign/likely benign/of uncertain significance (n = 74). This category includes some homozygous (n = 10) or compound heterozygous variants (n = 11). They are presenting with minor allele frequency (MAF) below 0.00002 (i.e., lower than C1-INH-HAE frequency), and may be quantitatively unable to cause haploinsufficiency. Rare benign variants could contribute as disease modifiers. Gonadal mosaicism in C1-INH-HAE is rare and must be distinguished from a de novo variant. Situations with paternal or maternal disomy have been recorded (n = 3). Genotypes must be interpreted with biological investigation fitting with C1-INH expression and typing. Any SERPING1 variant reminiscent of the dysfunctional phenotype of serpin with multimerization or latency should be identified as serpinopathy.

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Paternal mosaicism and hereditary angioedema in a Taiwanese family

Cited by 6 publications

References 11 publications

The genetics of hereditary angioedema: A review

The genetics of hereditary angioedema: A review

Distribution, clinical features and treatment in Taiwanese patients with symptomatic primary immunodeficiency diseases (PIDs) in a nationwide population-based study during 1985–2010

SERPING1 Variants and C1-INH Biological Function: A Close Relationship With C1-INH-HAE

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