First Report of Two Egyptian Patients with Desbuquois Dysplasia due to Homozygous <b><i>CANT1</i></b> Mutations

Abstract

Desbuquois dysplasia type 1 (DBQD1) is a very rare skeletal dysplasia characterized by growth retardation, short stature, distinct hand features, and a characteristic radiological monkey wrench appearance at the proximal femur. We report on 2unrelated Egyptian patients having the characteristic features of DBQD1 with different expressivity. Patient 1 presented at the age of 45 days with respiratory distress, short limbs, faltering growth, and distinctive facies while patient 2 presented at 5 years of age with short stature and hypospadias. The 2 patients shared radiological features suggestive of DBQD1. Whole-exome sequencing revealed a homozygous frameshift mutation in the &lt;i&gt;CANT1&lt;/i&gt; gene (NM_001159772.1:c.277_278delCT; p.Leu93ValfsTer89) in patient 1 and a homozygous missense mutation (NM_138793.4:c.898C&amp;#x3e;T; p.Arg300Cys) in patient 2. Phenotypic variability and variable expressivity of DBQD was evident in our patients. Hypoplastic scrotum and hypospadias were additional unreported associated findings, thus expanding the phenotypic spectrum of the disorder. We reviewed the main features of skeletal dysplasias exhibiting similar radiological manifestations for differential diagnosis. We suggest that the variable severity in both patients could be due to the nature of the &lt;i&gt;CANT1&lt;/i&gt; gene mutations which necessitates the molecular study of more cases for phenotype-genotype correlations.

Deficiency of Fam20b-Catalyzed Glycosaminoglycan Chain Synthesis in Neural Crest Leads to Cleft Palate

“…In the latest report, two lethal composite heterozygous variants in FAM20B (NM_014864 c.174_178delTACCT p.T59Afs*19/c.1038delG p.N347Mfs*4) were identified in a newborn who died soon after birth [41] and who suffered from a spectrum of defects highly similar to the autosomal recessive heterogeneous disorder, Desbuquois dysplasia (DBQD), which was characterized by joint laxity and skeletal change [53][54][55][56]. Several cases of DBQD have exhibited dysmorphic facial features, such as midface hypoplasia, flat nasal bridge, micrognathia, and cleft palate [57,58], resembling Pierre-Robin sequence and Wnt1-Cre; Fam20b f/f defects. Up to now, calcium-activated nucleotidase 1 gene (CANT1) and xylosyltransferase 1 (XYLT1) gene have been identified as the causative genes of DBQD [58,59].…”

A case of bilateral dislocation of knees: Desbuquois dysplasia Kim variant

“…While mutations in XYLT1 are responsible for some cases of DBQD type 2 1 , the underlying cause in the majority of cases is still unknown. The condition follows an autosomal recessive pattern of inheritance 3 . Breathing difficulties of a severe nature have been linked to type 1 4 .…”

Genomics in Egypt: Current Status and Future Aspects

“…It is noteworthy that there are continuous international collaborations between the aforementioned Institutions; NRC and MRI and research teams worldwide in attempt to reach the correct diagnosis and unravel the etiology and pathogenesis of rare disorders and identify causative mutations implicated in rare genetic syndromes. These research studies are either conducted on a cohort or per individual case and many of the past studies solved many cases and led to very promising and interesting results in the studied rare genetic syndromes in different genetic subspecialities; neuromuscular disorders, growth disorders, ciliopathies, ocular anomalies, congenital heart diseases, skeletal disorders, dental genetic abnormalities, inherited metabolic disorders, craniofacial disorders, dermatological anomalies and other variable rare genetic disorders with multiple congenital anomalies or disorders with underlying chromosomal aberrations or microdeletions ( Toomes et al, 1999 ; Zaki et al, 2007 ; Bielas et al, 2009 ; Handley et al, 2013 ; Rice et al, 2013 ; Traverso et al, 2013 ; Abdalla et al, 2014 ; Novarino et al, 2014 ; Abdalla et al, 2015 ; El-Hattab et al, 2016 ; Scott et al, 2016 ; Seifi et al, 2016 ; Abdalla et al, 2017 ; Fassad et al, 2018 ; Maddirevula et al, 2018 ; Patel et al, 2018 ; Fassad et al, 2020a ; Fassad et al, 2020b ; Chatron et al, 2020 ; Nabil et al, 2020 ; Shamseldin et al, 2020 ; Donato et al, 2021 ; Essawi et al, 2021 ; Horn et al, 2021 ; Meyer et al, 2021 ; Patel et al, 2021 ; Thomas et al, 2021 ). Moreover, several clinical genetic studies on categories of syndromes or rare disorders were conducted in Egypt.…”