Identification of biallelic EXTL3 mutations in a novel type of spondylo-epi-metaphyseal dysplasia | Semantic Scholar (2024)

The 15 th case of ISDNA (third patient of an Indian ancestry) in the world is reported, along with a review of literature, which finds that the affected individuals show abnormalities primarily in three systems namely- skeletal, nervous and immune system.

A new patient who is currently 15 years old in whom cystic liver lesions were detected in the prenatal period is reported, and a previously reported hom*ozygous missense variant in exon 3 c.953C > T; p.(Pro318Leu) in EXTL3 is revealed.

It is suggested that bi-allelic loss of function variants of TBX6 cause a spectrum of phenotypes including CS and SCD, depending on the severity of the loss ofTBX6 function.

This review focuses on genetic and glycobiological studies of chondrodysplasias with multiple dislocations associated with glycosaminoglycan biosynthesis defects and related animal models.

In these years of development, many pathogenic variants in genetic diseases with genetic and phenotypic heterogeneity have been investigated using whole‐exome sequencing (WES) technology.

Analysis of the data of 74 previously reported patients who carried various NBAS mutations demonstrated that although the most severe form of liver disease seems to require disruption of the N-terminal or middle part of NBAS, mutations of variable localizations in the gene have been associated with some form of Liver disease, as well as immunological disorders.

This study describes a patient with autosomal recessive osteopetrosis due to biallelic pathogenic variants in SLC4A2 and proves that the variants lead to SLC3A2 dysfunction, which altogether supports the importance of SLC 4A2 in human osteoclast differentiation.

ISDNA should be kept in mind in the differential diagnosis of patients presenting with neuro-immuno-skeletal dysplasia phenotype and had a hom*ozygous pathogenic mutation in EXTL3 gene.

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A second LRRK1 mutation is reported in Indian sibs with OSMD that had hom*ozygous mutation that produces an elongated mutant protein similar to the first case and further support that L RRK1 would cause a subset of OSMD cases.

The skeletal phenotype of this patient was milder than those of previously reported cases with NEK1 mutations and those with axial SMD harboring C21orf2 mutations, and the phenotype–genotype corelation in skeletal ciliopathies is challenging.

A clinically undiagnosed patient with GAN1 caused by segmental maternal UPiD with a hom*ozygous splice-site mutation in GAN is presented, which is readily detected by whole-exome sequencing (WES).

Data identify EXTL3 mutations as a novel cause of severe immune deficiency with skeletal dysplasia and developmental delay and underline a crucial role of HS in thymopoiesis and skeletal and brain development.

The nosology can also serve as a reference for the creation of locus‐specific databases that are expected to help in delineating genotype–phenotype correlations and to harbor the information that will be gained by combining clinical observations and next generation sequencing results.

The disrupted gene encoding of perlecan is disrupted in mice and abnormal phenotypes of the Hspg2 –/– skeleton are similar to those of thanatophoric dysplasia (TD) type I, which is caused by activating mutations in FGFR3 (refs 7, 8, 9), and to Those of Fgfr3 gain-of-function mice.

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