A novel homozygous missense variant in MATN3 causes spondylo-epimetaphyseal dysplasia Matrilin 3 type in a consanguineous family

Spondylo-epimetaphyseal dysplasia Matrilin 3 type (SEMD) is a rare autosomal recessive skeletal dysplasia characterized by short stature, abnormalities in the vertebral bodies and long bones, especially the lower limbs. We enrolled a consanguineous family from Pakistan in which multiple siblings suf...

Full description

Saved in:
Bibliographic Details
Published in:European journal of medical genetics 2020-08, Vol.63 (8), p.103958-103958, Article 103958
Main Authors: Yasin, Samina, Mustafa, Saima, Ayesha, Arzoo, Latif, Muhammad, Hassan, Mubashir, Faisal, Muhammad, Makitie, Outi, Iqbal, Furhan, Naz, Sadaf
Format: Article
Language:English
Subjects:
Consanguinity
Exome sequencing
Female
Homozygote
Humans
Male
Matrilin Proteins - chemistry
Matrilin Proteins - genetics
Medicin och hälsovetenskap
Mutation, Missense
Osteochondrodysplasias - genetics
Osteochondrodysplasias - pathology
Pakistan
Pedigree
Protein Domains
SEMD
Short stature
Skeletal dysplasia
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Spondylo-epimetaphyseal dysplasia Matrilin 3 type (SEMD) is a rare autosomal recessive skeletal dysplasia characterized by short stature, abnormalities in the vertebral bodies and long bones, especially the lower limbs. We enrolled a consanguineous family from Pakistan in which multiple siblings suffered from severe skeletal dysplasia. The six affected subjects ranged in heights from 100 to 136 cm (~-6 standard deviation). Lower limb abnormalities with variable varus and valgus deformities and joint dysplasia were predominant features of the clinical presentation. Whole exome sequencing (WES) followed by Sanger sequencing identified a missense variant, c.542G > A, p.(Arg181Gln) in MATN3 as the genetic cause of the disorder. The variant was homozygous in all affected individuals while the obligate carriers had normal heights with no skeletal symptoms, consistent with a recessive pattern of inheritance. Multiple sequence alignment revealed that MATN3 domain affected by the variant is highly conserved in orthologous proteins. The c.542G > A, p.(Arg181Gln) variant is only the fourth variant in MATN3 causing an autosomal recessive disorder and thus expands the genotypic spectrum. •We describe a novel homozygous variant in MATN3.•Biallelic MATN3 variant causes SEMD in six patients of a family.•The carriers had no skeletal abnormalities, ruling out dominantly inherited MED.•This is only the fourth report of SEMD due to MATN3 variant.
ISSN:1769-7212
1878-0849
1878-0849
DOI:10.1016/j.ejmg.2020.103958