Short Communication - A Missense Mutation in COL10A1 Gene in a Pakistani Consanguineous Family with Schmid Type Metaphyseal Chondrodysplasia

Schmid-type metaphyseal chondrodysplasia (MCDS) is an autosomal dominant disorder caused by COL10A1 mutations and is characterized by short stature, waddling gait, coxa vara and bowing of the long bones. A large family from Southern Punjab in Pakistan suffering from MCDS following autosomal dominant...

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Bibliographic Details
Published in:Pakistan journal of zoology 2022-06, Vol.54 (3), p.1447
Main Authors: Mustafa, Saima, Bukhari, firdous, Aftab, Muhammad Nazar, Asif, Muhammad, Amjad, Muhammad, Ijaz, Maryam, Latif, Muhammad, Iqbal, Furhan
Format: Article
Language:English
Subjects:
Abnormalities
Alleles
Amino acid sequence
Amino acids
Amplification
Biomedical materials
Blood
Body weight
Bone dysplasia
Bones
Bowing
Causes of
Chondrocytes
Chondrodysplasia punctata
Chondrodystrophy
Collagen
Collagen (type X)
Conflicts of interest
Consents
Copy number
Coxa
Data analysis
Deletion
Denaturation
Deoxyribonucleic acid
DNA
Domains
Dwarfism
Electrophoresis
Endochondral bone
Ethical standards
Ethylenediaminetetraacetic acids
Etiology
Gait
Gene mutations
Genetic aspects
Genotype & phenotype
Hematopoiesis
Hereditary diseases
Heredity
Human population genetics
Limbs
Medical research
Medicine, Experimental
Mineralization
Missense mutation
Mutation
Nucleotide sequence
Nucleotides
Osteoarthritis
Patients
Phenotypes
Proteins
Radiography
Siblings
Skeleton
Vertebrates
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Summary:Schmid-type metaphyseal chondrodysplasia (MCDS) is an autosomal dominant disorder caused by COL10A1 mutations and is characterized by short stature, waddling gait, coxa vara and bowing of the long bones. A large family from Southern Punjab in Pakistan suffering from MCDS following autosomal dominant mode of inheritance were enrolled in present study. Whole exome sequencing (WES) approach was adopted to identify causative agent of dwarfism that reveled a previously reported a missense mutation (c.2011 A > G, p.Ser 671Pro) in exon 3 of COL10A1 gene. Sanger sequencing confirmed these mutations in all enrolled subjects and mutation followed Mendalian pattern of inheritance. Multiple sequence alignment by Clustal Omega revealed that domain of COL10A1 containing mutations is highly conserved. In conclusion, we are reporting a previously reported a missense mutation in COL10A1 gene that is causing MCDS in a large consanguineous Pakistani family. Keywords: Schmid-type metaphyseal chondrodysplasia, WES, Sanger sequencing The metaphyseal chondrodysplasias are clinically and etiologically heterogeneous (hall, 2002). Among them, metaphyseal chondrodysplasia Schmid type (SMCD; MIM# 156500) has been identified as the most common type of metaphyseal chondrodysplasia (Bateman et al., 2005). The radiographic features of SMCD are metaphyseal abnormality, including widening, sclerosis and irregularity. The distal femoral and proximal tibial metaphyses are the most consistently and severely affected. Coxa vara frequently in association with mild femoral bowing is also observed in the majority of cases and is an important radiographic sign in differentiating SMCD from other forms of metaphyseal chondrodysplasia (hall, 2002). We enrolled a consanguineous dwarf family with typical MCDS syndromes from Pakistan and used whole exome sequencing (WES) approach to identify the variant(s) associated with MCDS. here we report that MCDS in this family was due to a known missense point mutation in COL10A1 gene. Materials and methods A dwarf family was enrolled from Ranjanpur District in Punjab (Pakistan) having multiple siblings suffering from short stature. Subjects were diagnosed to be suffering from metaphyseal chondrodysplasia Schmid type (MCDS) by a medical specialist. The ethical committee at Bahauddin Zakariya University, Multan approved this research. Written informed consents were obtained for all participants. Ten blood samples were collected from family including eight patients
ISSN:0030-9923