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. 2020 Dec;7(4):109-112.
doi: 10.1055/s-0041-1722873. Epub 2021 Feb 1.

Further Evidence of a Recessive Variant in COL1A1 as an Underlying Cause of Ehlers-Danlos Syndrome: A Report of a Saudi Founder Mutation

Ahmad Almatrafi  1 , Jamil A Hashmi  2 , Fatima Fadhli  3 , Asma Alharbi  2 , Sibtain Afzal  4 , Khushnooda Ramzan  5 , Sulman Basit  2
Affiliations

Further Evidence of a Recessive Variant in COL1A1 as an Underlying Cause of Ehlers-Danlos Syndrome: A Report of a Saudi Founder Mutation

Ahmad Almatrafi et al. Glob Med Genet. 2020 Dec.

Abstract

Ehlers-Danlos syndrome (EDS) is a group of clinically and genetically heterogeneous disorder of soft connective tissues. The hallmark clinical features of the EDS are hyperextensible skin, hypermobile joints, and fragile vessels. It exhibits associated symptoms including contractures of muscles, kyphoscoliosis, spondylodysplasia, dermatosparaxis, periodontitis, and arthrochalasia. The aim of this study is to determine the exact subtype of EDS by molecular genetic testing in a family segregating EDS in an autosomal recessive manner. Herein, we describe a family with two individuals afflicted with EDS. Whole exome sequencing identified a homozygous missense mutation (c.2050G > A; p.Glu684Lys) in the COL1A1 gene in both affected individuals, although heterozygous variants in the COL1A1 are known to cause EDS. Recently, only one report showed homozygous variant as an underlying cause of the EDS in two Saudi families. This is the second report of a homozygous variant in the COL1A1 gene in a family of Saudi origin. Heterozygous carriers of COL1A1 variant are asymptomatic. Interestingly, the homozygous variant identified previously and the one identified in this study are same (c.2050G > A). The identification of a unique homozygous mutation (c.2050G > A) in three Saudi families argues in favor of a founder effect.

Keywords: COL1A1 homozygous mutation; Ehlers–Danlos syndrome; Saudi family; founder mutation.

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Conflict of interest statement

Conflict of Interest None declared.

Figures

Fig. 1
Fig. 1
( A ) Pedigree of the family investigated in the present study showing autosomal recessive inheritance pattern. Double lines indicate consanguineous marriages. Filled symbols represent affected individuals. ( B, C ) Partial sequence of the exon 31 of the COL1A1 gene obtained by Sanger sequencing. Upper panel ( B ) shows chromatogram of the carrier and lower panel ( C ) shows chromatogram of the affected individuals of the family. Red arrow indicates the position of the mutation.
See this image and copyright information in PMC

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