Family CL-16: FamilyInfo: Japanese and German ancestry Proband II.2: had large aneurysm of sinuses of Valsalva and ascending aorta at ae 38 skin laxity on lower face and submandibular area during childhood but not noticeable in adulthood single palmar crease bilateral limited ability to supinate forearms inguinal hernia

II.3: died at age 26 of aortic dissection, no skin laxity

I.1, III.1: mildly dilated aortic root, mild aortic insufficiency, cutis laxa (face, submandibular, trunk, extremities) III.1: overall normal pulmonary function, prolonged wound healing I.1: inguinal hernia III.1: 12 year old male

VariantInfo: Direct sequence analysis of ELN in CL‐16, III.1 uncovered a 25 bp deletion in exon 30, 2114_2138del. This defect was present in all affected members of the family available for testing, including I.1 and II.2. The mutation was not found in II.1. CAID: CA322210

Family CL-13: Singaporean girl of chinese decent with no family history of cutis laxa.

MonDO: MONDO:0008504

Case: CL-13, II.1: 6 year old Asian female, Singaporean of Chinese decent with de novo variant.

DiseaseAssertion: Cutis Laxa

FamilyInfo: Parents do not harbor variant and are asymptomatic. No family history of cutis laxa.

CasePresentingHPOs: HP:0000973, HP:0001582, HP:0008070, HP:0040080, HP:0000343, HP:0005280, HP:0002616 (Cutis laxa, Redundant skin, Sparse hair, Anteverted ears, Depressed nasal bridge, Aortic root aneurysm)

CaseHPOFreeText: tear shaped eyes

CaseNOTHPOs: HP:0001659 (Aortic regurgitation)

CasePreviousTesting: At the age of 5 years 9 months an echocardiogram showed significant dilatation of the aortic root at the level of the sinuses of Valsalva with a measured diameter of 2.47 cm (normal <2.2 cm for her body surface area).

GenotypingMethod: DNA extracted from whole blood was amplified using PCR for each exon of ELN gene. Amplified products were sequenced bidirectionally using Sanger sequencing. A panel of 121 normal control individuals was genotyped for mutations 2114_2138del and 2159delC using denaturing high performance liquid chromatography.

Variant: ELN:c.2159delC, in exon30 ClinVarID: 16736 CAID: CA2580077344 gnomAD: Not found in gnomAD v.4.1

Family CL-16: FamilyInfo: Japanese and German ancestry Proband II.2: had large aneurysm of sinuses of Valsalva and ascending aorta at ae 38 skin laxity on lower face and submandibular area during childhood but not noticeable in adulthood single palmar crease bilateral limited ability to supinate forearms inguinal hernia

II.3: died at age 26 of aortic dissection, no skin laxity

I.1, III.1: mildly dilated aortic root, mild aortic insufficiency, cutis laxa (face, submandibular, trunk, extremities) III.1: overall normal pulmonary function, prolonged wound healing I.1: inguinal hernia III.1: 12 year old male

VariantInfo: Direct sequence analysis of ELN in CL‐16, III.1 uncovered a 25 bp deletion in exon 30, 2114_2138del. This defect was present in all affected members of the family available for testing, including I.1 and II.2. The mutation was not found in II.1. CAID: CA322210

Family CL-13: Singaporean girl of chinese decent with no family history of cutis laxa.

MonDO: MONDO:0008504

Case: CL-13, II.1: 6 year old Asian female, Singaporean of Chinese decent with de novo variant.

DiseaseAssertion: Cutis Laxa

FamilyInfo: Parents do not harbor variant and are asymptomatic. No family history of cutis laxa.

CasePresentingHPOs: HP:0000973, HP:0001582, HP:0008070, HP:0040080, HP:0000343, HP:0005280, HP:0002616 (Cutis laxa, Redundant skin, Sparse hair, Anteverted ears, Depressed nasal bridge, Aortic root aneurysm)

CaseHPOFreeText: tear shaped eyes

CaseNOTHPOs: HP:0001659 (Aortic regurgitation)

CasePreviousTesting: At the age of 5 years 9 months an echocardiogram showed significant dilatation of the aortic root at the level of the sinuses of Valsalva with a measured diameter of 2.47 cm (normal <2.2 cm for her body surface area).

GenotypingMethod: DNA extracted from whole blood was amplified using PCR for each exon of ELN gene. Amplified products were sequenced bidirectionally using Sanger sequencing. A panel of 121 normal control individuals was genotyped for mutations 2114_2138del and 2159delC using denaturing high performance liquid chromatography.

Variant: ELN:c.2159delC, in exon30 ClinVarID: 16736 CAID: CA2580077344 gnomAD: Not found in gnomAD v.4.1