Disease #06980 (HAE4 (angioedema, hereditary, type 4), OMIM:619360)

Official abbreviation	HAE4
Name	angioedema, hereditary, type 4
OMIM ID	619360
Human Phenotype Ontology Project (HPO)	HPO
Inheritance	Autosomal dominant
Individuals reported having this disease	25
Phenotype entries for this disease	12
Associated with 1 gene	PLG
Associated tissues	-
Disease features	-
Remarks	-
Date created	2022-11-30 10:47:35 +01:00 (CET)
Date last edited	N/A

Individuals

Legend

Please note that a short description of a certain column can be displayed when you move your mouse cursor over the column's header and hold it still. Below, a more detailed description is shown per column.

ID_report: ID of the individual that can be publically shared, e.g. as listed in a publication

Reference: reference to publication describing the individual/family, possibly giving more phenotypic details than listed in this database entry, incl. link to PubMed or other source, e.g. "den Dunnen ASHG2003 P2346"

Remarks: remarks about the individual

Gender: gender individual
All options:

? = unknown
- = not applicable
F = female
M = male
rF = raised as female
rM = raised as male

Consanguinity: indicates whether the parents are related (consanguineous), not related (non-consanguineous) or whether consanguinity is not known (unknown)
All options:

no = non-consanguineous parents
yes = consanguineous parents
likely = consanguinity likely
? = unknown
- = not applicable

Country: where (country) does the individual live/recently came from. Give additional details (population, specific sub-group) and when parents come from different countries in "Population". Belgium = individual lives in/recently came from Belgium, (France) = reported by laboratory in France, individual's country of origin not sure
All options:

? (unknown)
- (not applicable)
Afghanistan
(Afghanistan)
Albania
(Albania)
Algeria
(Algeria)
American Samoa
(American Samoa)
Andorra
(Andorra)
Angola
(Angola)
Anguilla
(Anguilla)
Antarctica
(Antarctica)
Antigua and Barbuda
(Antigua and Barbuda)
Argentina
(Argentina)
Armenia
(Armenia)
Aruba
(Aruba)
Australia
(Australia)
Austria
(Austria)
Azerbaijan
(Azerbaijan)
Bahamas
(Bahamas)
Bahrain
(Bahrain)
Bangladesh
(Bangladesh)
Barbados
(Barbados)
Belarus
(Belarus)
Belgium
(Belgium)
Belize
(Belize)
Benin
(Benin)
Bermuda
(Bermuda)
Bhutan
(Bhutan)
Bolivia
(Bolivia)
Bosnia and Herzegovina
(Bosnia and Herzegovina)
Botswana
(Botswana)
Bouvet Island
(Bouvet Island)
Brazil
(Brazil)
British Indian Ocean Territory
(British Indian Ocean Territory)
Brunei Darussalam
(Brunei Darussalam)
Bulgaria
(Bulgaria)
Burkina Faso
(Burkina Faso)
Burundi
(Burundi)
Cambodia
(Cambodia)
Cameroon
(Cameroon)
Canada
(Canada)
Cape Verde
(Cape Verde)
Cayman Islands
(Cayman Islands)
Central African Republic
(Central African Republic)
Central Europe
Chad
(Chad)
Chile
(Chile)
China
(China)
Christmas Island
(Christmas Island)
Cocos (Keeling Islands)
(Cocos (Keeling Islands))
Colombia
(Colombia)
Comoros
(Comoros)
Congo
(Congo)
Cook Islands
(Cook Islands)
Costa Rica
(Costa Rica)
Cote D'Ivoire (Ivory Coast)
(Cote D'Ivoire (Ivory Coast))
Croatia (Hrvatska)
(Croatia (Hrvatska))
Cuba
(Cuba)
Cyprus
(Cyprus)
Czech Republic
(Czech Republic)
Denmark
(Denmark)
Djibouti
(Djibouti)
Dominica
(Dominica)
Dominican Republic
(Dominican Republic)
East Timor
(East Timor)
Ecuador
(Ecuador)
Egypt
(Egypt)
El Salvador
(El Salvador)
England
(England)
Equatorial Guinea
(Equatorial Guinea)
Eritrea
(Eritrea)
Estonia
(Estonia)
Ethiopia
(Ethiopia)
Falkland Islands (Malvinas)
(Falkland Islands (Malvinas))
Faroe Islands
(Faroe Islands)
Fiji
(Fiji)
Finland
(Finland)
France
(France)
Gabon
(Gabon)
Gambia
(Gambia)
Georgia
(Georgia)
Germany
(Germany)
Ghana
(Ghana)
Gibraltar
(Gibraltar)
Greece
(Greece)
Greenland
(Greenland)
Grenada
(Grenada)
Guadeloupe
(Guadeloupe)
Guam
(Guam)
Guatemala
(Guatemala)
Guiana, French
(Guiana, French)
Guinea
(Guinea)
Guinea-Bissau
(Guinea-Bissau)
Guyana
(Guyana)
Haiti
(Haiti)
Heard and McDonald Islands
(Heard and McDonald Islands)
Honduras
(Honduras)
Hong Kong
(Hong Kong)
Hungary
(Hungary)
Iceland
(Iceland)
India
(India)
Indonesia
(Indonesia)
Iran
(Iran)
Iraq
(Iraq)
Ireland
(Ireland)
Israel
(Israel)
Italy
(Italy)
Jamaica
(Jamaica)
Japan
(Japan)
Jordan
(Jordan)
Kazakhstan
(Kazakhstan)
Kenya
(Kenya)
Kiribati
(Kiribati)
Korea
(Korea)
Korea, North (People's Republic)
(Korea, North (People's Republic))
Korea, South (Republic)
(Korea, South (Republic))
Kosovo
(Kosovo)
Kuwait
(Kuwait)
Kyrgyzstan (Kyrgyz Republic)
(Kyrgyzstan (Kyrgyz Republic))
Laos
(Laos)
Latvia
(Latvia)
Lebanon
(Lebanon)
Lesotho
(Lesotho)
Liberia
(Liberia)
Libya
(Libya)
Liechtenstein
(Liechtenstein)
Lithuania
(Lithuania)
Luxembourg
(Luxembourg)
Macau
(Macau)
Macedonia
(Macedonia)
Madagascar
(Madagascar)
Malawi
(Malawi)
Malaysia
(Malaysia)
Maldives
(Maldives)
Mali
(Mali)
Mallorca
(Mallorca)
Malta
(Malta)
Marshall Islands
(Marshall Islands)
Martinique
(Martinique)
Mauritania
(Mauritania)
Mauritius
(Mauritius)
Mayotte
(Mayotte)
Mexico
(Mexico)
Micronesia
(Micronesia)
Moldova
(Moldova)
Monaco
(Monaco)
Mongolia
(Mongolia)
Montserrat
(Montserrat)
Morocco
(Morocco)
Mozambique
(Mozambique)
Myanmar
(Myanmar)
Namibia
(Namibia)
Nauru
(Nauru)
Nepal
(Nepal)
Netherlands
(Netherlands)
Netherlands Antilles
(Netherlands Antilles)
Neutral Zone (Saudia Arabia/Iraq)
(Neutral Zone (Saudia Arabia/Iraq))
New Caledonia
(New Caledonia)
New Zealand
(New Zealand)
Nicaragua
(Nicaragua)
Niger
(Niger)
Nigeria
(Nigeria)
Niue
(Niue)
Norfolk Island
(Norfolk Island)
Northern Ireland
(Northern Ireland)
Northern Mariana Islands
(Northern Mariana Islands)
Norway
(Norway)
Oman
(Oman)
Pakistan
(Pakistan)
Palau
(Palau)
Palestine
(Palestine)
Panama
(Panama)
Papua New Guinea
(Papua New Guinea)
Paraguay
(Paraguay)
Peru
(Peru)
Philippines
(Philippines)
Pitcairn
(Pitcairn)
Poland
(Poland)
Polynesia, French
(Polynesia, French)
Portugal
(Portugal)
Puerto Rico
(Puerto Rico)
Qatar
(Qatar)
Reunion
(Reunion)
Romania
(Romania)
Russia
(Russia)
Russian Federation
(Russian Federation)
Rwanda
(Rwanda)
S. Georgia and S. Sandwich Isls.
(S. Georgia and S. Sandwich Isls.)
Saint Kitts and Nevis
(Saint Kitts and Nevis)
Saint Lucia
(Saint Lucia)
Saint Vincent and The Grenadines
(Saint Vincent and The Grenadines)
Samoa
(Samoa)
San Marino
(San Marino)
Sao Tome and Principe
(Sao Tome and Principe)
Saudi Arabia
(Saudi Arabia)
Scotland
(Scotland)
Senegal
(Senegal)
Serbia
(Serbia)
Seychelles
(Seychelles)
Sierra Leone
(Sierra Leone)
Singapore
(Singapore)
Slovakia (Slovak Republic)
(Slovakia (Slovak Republic))
Slovenia
(Slovenia)
Solomon Islands
(Solomon Islands)
Somalia
(Somalia)
South Africa
(South Africa)
Southern Territories, French
(Southern Territories, French)
Soviet Union (former)
(Soviet Union (former))
Spain
(Spain)
Sri Lanka
(Sri Lanka)
St. Helena, Ascension and Tristan da
Cunha
(St. Helena, Ascension and Tristan da
Cunha)
St. Pierre and Miquelon
(St. Pierre and Miquelon)
Sudan
(Sudan)
Sudan, South
(Sudan, South)
Suriname
(Suriname)
Svalbard and Jan Mayen Islands
(Svalbard and Jan Mayen Islands)
Swaziland
(Swaziland)
Sweden
(Sweden)
Switzerland
(Switzerland)
Syria
(Syria)
Taiwan
(Taiwan)
Tajikistan
(Tajikistan)
Tanzania
(Tanzania)
Thailand
(Thailand)
Togo
(Togo)
Tokelau
(Tokelau)
Tonga
(Tonga)
Trinidad and Tobago
(Trinidad and Tobago)
Tunisia
(Tunisia)
Turkey
(Turkey)
Turkmenistan
(Turkmenistan)
Turks and Caicos Islands
(Turks and Caicos Islands)
Tuvalu
(Tuvalu)
Uganda
(Uganda)
Ukraine
(Ukraine)
United Arab Emirates
(United Arab Emirates)
United Kingdom (Great Britain)
(United Kingdom (Great Britain))
United States
(United States)
Uruguay
(Uruguay)
US Minor Outlying Islands
(US Minor Outlying Islands)
Uzbekistan
(Uzbekistan)
Vanuatu
(Vanuatu)
Vatican City State (Holy See)
(Vatican City State (Holy See))
Venezuela
(Venezuela)
Viet Nam
(Viet Nam)
Virgin Islands (British)
(Virgin Islands (British))
Virgin Islands (US)
(Virgin Islands (US))
Wales
(Wales)
Wallis and Futuna Islands
(Wallis and Futuna Islands)
Western Sahara
(Western Sahara)
Yemen
(Yemen)
Yugoslavia
(Yugoslavia)
Zaire
(Zaire)
Zambia
(Zambia)
Zimbabwe
(Zimbabwe)

Population: population the individual (or ancestors) belongs to; e.g. white, gypsy, Jewish-Ashkenazi, Africa-N, Sardinia, etc.

Age at death: age at which the individual deceased (when applicable):

35y = 35 years
>43y = still alive at 43y
04y08m = 4 years and 8 months
00y00m01d12h = 1 day and 12 hours
18y? = around 18 years
30y-40y = between 30 and 40 years
>54y = older than 54
? = unknown

VIP: individual/phenotype VIP-status was requested for matchmaking - need collaboration(s) to crack the case - please contact the submitter/curator. NOTE: to get VIP status ask the curator.

Data_av: are additional data available upon request: e.g. pedigree (yes/no/?)

Treatment: treatment of patient

Variants in genes: The individual has variants for this gene.

Panel size: Number of individuals this entry represents; e.g. 1 for an individual, 5 for a family with 5 affected members.

How to query this table

All list views have search fields which can be used to search data. You can search for a complete word or you can search for a part of a search term. If you enclose two or more words in double quotes, LOVD will search for the combination of those words only exactly in the order you specify. Note that search terms are case-insensitive and that wildcards such as * are treated as normal text! For all options, like "and", "or", and "not" searches, or searching for prefixes or suffixes, see the table below.

Operator	Column type	Example	Matches
	Text	Arg	all entries containing 'Arg'
space	Text	Arg Ser	all entries containing 'Arg' and 'Ser'
\|	Text	Arg\|Ser	all entries containing 'Arg' or 'Ser'
!	Text	!fs	all entries not containing 'fs'
^	Text	^p.(Arg	all entries beginning with 'p.(Arg'
$	Text	Ser)$	all entries ending with 'Ser)'
=""	Text	=""	all entries with this field empty
=""	Text	="p.0"	all entries exactly matching 'p.0'
!=""	Text	!=""	all entries with this field not empty
!=""	Text	!="p.0"	all entries not exactly matching 'p.0?'
combination	Text	*\|Ter !fs	all entries containing '*' or 'Ter' but not containing 'fs'
	Date	2020	all entries matching the year 2020
\|	Date	2020-03\|2020-04	all entries matching March or April, 2020
!	Date	!2020-03	all entries not matching March, 2020
<	Date	<2020	all entries before the year 2020
<=	Date	<=2020-06	all entries in or before June, 2020
>	Date	>2020-06	all entries after June, 2020
>=	Date	>=2020-06-15	all entries on or after June 15th, 2020
combination	Date	2019\|2020 <2020-03	all entries in 2019 or 2020, and before March, 2020
	Numeric	23	all entries exactly matching 23
\|	Numeric	23\|24	all entries exactly matching 23 or 24
!	Numeric	!23	all entries not exactly matching 23
<	Numeric	<23	all entries lower than 23
<=	Numeric	<=23	all entries lower than, or equal to, 23
>	Numeric	>23	all entries higher than 23
>=	Numeric	>=23	all entries higher than, or equal to, 23
combination	Numeric	>=20 <30 !23	all entries with values from 20 to 29, but not equal to 23

Some more advanced examples:

Example	Matches
Asian	all entries containing 'Asian', 'asian', including 'Caucasian', 'caucasian', etc.
Asian !Caucasian	all entries containing 'Asian' but not containing 'Caucasian'
Asian\|African !Caucasian	all entries containing 'Asian' or 'African', but not containing 'Caucasian'
"South Asian"	all entries containing 'South Asian', but not containing 'South East Asian'

To sort on a certain column, click on the column header or on the arrows. If that column is already selected to sort on, the sort order will be swapped. The column currently sorted on has a darker blue background color than the other columns. The up and down arrows next to the column name indicate the current sorting direction. When sorting on any field other than the default, LOVD will sort secondarily on the default sort column.

25 entries on 1 page. Showing entries 1 - 25.

Legend

How to query

Individual ID	ID_report	Reference	Remarks	Gender	Consanguinity	Country	Population	Age at death	VIP	Data_av	Treatment	Disease	Phenotype details	Genes screened	Variants in genes	Variants	Panel size	Owner
00361803	-	Journal: Bork 2020	One family with compound heterozygous individuals and 12 affected patients	-	-	Germany	-	-	-	-	-	HAE4	Proband presenting with a HAE with C1-INH deficiency	PLG	PLG, SERPING1	2	12	Christian Drouet
00361804	-	Journal: Bork 2018 Journal: Bork 2023 Journal: Hintze 2023	Bork 2018: Thirteen families with 60 affected individuals Bork 2023: Six German pedigrees have been found to carry a c.988A>G; solitary German carriers (n=6) Hintze 2023: a German pedigree with 8 affected individuals	-	no	Germany	-	-	-	-	-	HAE4	Probands presenting with a HAE-PLG phenotype with frequent macroglossia attacks	PLG	PLG	1	74	Christian Drouet
00361844	-	Journal: Germenis 2018	First family with a homozygous proband for a c.988A>G variant and 3 heterozygous carriers, incl one symptomatic female individual	-	-	Greece	-	-	-	-	-	HAE4	Proband presenting with a HAE phenotype	PLG	PLG	1	4	Christian Drouet
00361847	-	Journal: Germenis 2018	A single pedigree has been found as carrying a c.988A>G variant; the female proband is a homozygous carrier, 2 heterozygous carriers have been found asymptomatic.	F	?	Greece	-	-	-	-	-	HAE4	Proband presenting with a PLG-HAE phenotype	PLG	PLG	1	3	Christian Drouet
00361882	-	Journal: Parsopoulou 2020	A Spanish family with 5 heterozygous carriers of a c.988A>G variant, incl 3/5 symptomatic individuals	-	no	Spain	-	-	-	-	-	HAE4	Proband presenting with a HAE phenotype	PLG	PLG	1	3	Christian Drouet
00383163	-	Journal: Bodian 2019	-	F	-	United States	-	-	-	-	-	HAE4	Proband presenting with a nlC-INH-HAE presenting with lips and tongue angioedema, without wheels, and resistant to H1-antihistamines	PLG	PLG	1	1	Christian Drouet
00383164	-	Journal: Recke 2019	-	-	no	Germany	-	-	-	-	-	HAE4	6 affected individuals among 7 c.988A>G variant carriers within a German family, Proband presenting with nl-C1-INH-HAE and recurrent swellings of tongue and lips, sometimes also larynx, throat and upper airways	PLG	PLG	1	6	Christian Drouet
00383165	-	Journal: Belbezier 2018	Three kindreds have been reported as carrying a c.988A>G variant, with 12 affected individuals	-	no	France	-	-	-	-	-	HAE4	Probands presenting with a nl-C1-INH-HAE and face/tongue swelling episodes.	PLG	PLG	1	12	Christian Drouet
00385446	-	Journal: Farkas 2021	Hungarian pedigree with a single symptomatic carrier of a c.988A>G variant in the PLG gene	F	-	Hungary	-	-	-	-	-	HAE4	Proband presenting with an angioedema phenotype a the age of 17, then 20 years later, with an iatrogenic angioedema precipitated after intake of ACEi	PLG	PLG	1	1	Christian Drouet
00385447	-	Journal: Yakushiji 2018	Two Japanese pedigrees have been found as carrying a c.988A>G variant in the PLG gene Family 1 (n=2) Family 2 (n=2)	-	-	Japan	-	-	-	-	-	HAE4	Probands presenting with non histamine-mediated angioedema; two female symptomatic carriers are presenting with a recurrent macroglossia.	PLG	PLG	1	4	Christian Drouet
00385448	-	Journal: Germenis 2018	-	F	-	Bulgaria	-	-	-	-	-	HAE4	A single Bulgarian female patient presenting with a non histamine-dependent angioedema phenotype	PLG	PLG	1	1	Christian Drouet
00403772	-	Journal: Manto 2021	10 families, with 14 affected carriers, have been reported as carrying a PLG variant c.988A>G	-	-	Russia	-	-	-	-	-	HAE4	A HAE phenotype has been recorded by the authors within 10 families	PLG	PLG	1	14	Christian Drouet
00426343	FamPatII1	PubMed: Yakushiji 2023, Journal: Yakushiji 2023	3-generation family, 5 affected (4 female, 1 male); 3 carriers (1 female, 2 male) are asymptomatic	F	no	Japan	-	-	-	-	-	HAE4	see paper; ..., everely swollen tongue and lips	PLG	PLG	1	5	Christian Drouet
00433192	-	Journal: Hintze 2023	A female proband carrying both variants PLG c.988A>G;p.(lys330Glu) and F12 c.1681-1G>A; 6 compound heterozygous affected individuals, 2 heterozygous affected individuals carrying a PLG variant	F	-	Germany	-	-	-	-	-	HAE4	Proband presenting with a bradykinin-dependent HAE phenotype	PLG	F12, PLG	2	8	Christian Drouet
00435329	Fam1-3	Journal: Dewald 2018	Three independent pedigrees have been shown as carrying the variant Family 1 (n=9), Family 2 (n=4), Family 3 (n=9)	F	-	Germany	-	-	-	-	-	HAE4	Probands presenting with a bradykinin angioedema phenotype	PLG	PLG	1	22	Christian Drouet
00436344	-	Journal: Kiss 2013 PubMed: Kiss 2013	A HAE-PLG pedigree with 5 affected individuals, 3 female and 2 male	F	no	Hungary	-	-	-	-	-	HAE4	-	-	-	-	5	Christian Drouet
00436383	-	Journal: Nakayama 2023	Single individual	F	no	Japan	-	-	-	-	-	HAE4	Recurrent acute abdomen following low-dose oestrogen-progestin therapy	PLG	PLG	1	1	Christian Drouet
00436400	-	Journal: Katelaris 2023	-	F	-	Brazil	white (Italy)	-	-	-	-	HAE4	HAE-nC1-INH of the proband possibly triggered after taking ACEi (perindopril), but continues after stopping ACEi	PLG	PLG	1	2	Christian Drouet
00443695	-	Journal: Friedman 2023	A US family with a female proband is presenting with macroglossia, a mother with peripheral angioedema and a son died because of airway obstruction	F	-	United States	-	-	-	-	-	HAE4	Proband presenting with macroglossia, her mother with peripheral angioedema, her son with airway obstruction	PLG	PLG	1	3	Christian Drouet
00448539	-	Journal: Rozevska 2024	-	-	no	Latvia	-	-	-	-	-	HAE4	Proband presenting with a HAE-nC1-INH phenotype	PLG	PLG	1	1	Christian Drouet
00454850	-	Journal: Adatia 2024	-	-	-	Canada	-	-	-	-	-	HAE4	Proband presenting with a HAE-nC1INH phenotype	PLG	PLG	1	2	Christian Drouet
00464698	-	Journal: Sugimoto 2025	Single female individual affected	F	no	Japan	-	-	-	-	-	HAE4	Proband presenting with a HAE-PLG phenotype; recurrent acute abdominal pain after starting low-dose estrogen therapy.	PLG	PLG	1	1	Christian Drouet
00464707	-	Journal: Sugimoto 2025	A single family with two affected sisters	F	no	Japan	-	-	-	-	-	HAE4	Two affected sisters presenting with occasional abdominal pain and vomiting	PLG	PLG	1	2	Christian Drouet
00465619	-	Journal: de Albuquerque Campos 2023	-	F	no	Brazil	-	-	-	-	-	HAE4	Progressive sagging of the skin on the chest, abdomen and the face, with excessive wrinkling (cutis laxa). Development of facial angioedema after Zika virus infection with associated hives and skin swellings; poor improvement with H1-antihistamines treatment. Hives resolve after treatment with omalizumab but no change in frequency of angioedema.	PLG	PLG	1	1	Christian Drouet
00465622	-	Journal: Purina 2023	The first HAE-nC1INH patient from Latvia with identified pathogenic variant in the PLG gene.	F	no	Latvia	-	-	-	-	-	HAE4	Rare, irregular mild episodes of swelling in the extremities lasting several days and recurrent abdominal pain. At 30 years of age she had mild episodes of edema during pregnancy and while taking oral contraceptives. No family history.	PLG	PLG	1	1	Christian Drouet

Legend

How to query

Global Variome shared LOVD

HSPG2 (heparan sulfate proteoglycan 2)