A novel missense mutation of CRYGS underlies congenital cataract in a Chinese family

Chemical Properties Determine Solubility and Stability in βγ‐Crystallins of the Eye Lens

“…[115] The HγS-Y67N, was recently discovered in a Chinese family with autosomal dominant nuclear congenital cataracts. [116] In this protein, structural destabilization leading to reduced thermal and chemical stability relative to HγS-WT [117] takes the form of disrupting one of the tyrosine corners that are essential for stabilizing Greek key motifs. [106] Another example of this unfolding mechanism was found in the zebrafish γM7 crystallin, which has a CTD that is highly similar to that of HγS and, in contrast, an N-terminus with key sequence differences, especially between residues 67-72.…”

“…In a cataract‐related variant of mouse γS‐crystallin, a single mutation, F9S in the first β‐strand destabilizes the first Greek key motif, promoting unfolding of the NTD under even mild heat stress [115] . The HγS‐Y67N, was recently discovered in a Chinese family with autosomal dominant nuclear congenital cataracts [116] . In this protein, structural destabilization leading to reduced thermal and chemical stability relative to HγS‐WT [117] takes the form of disrupting one of the tyrosine corners that are essential for stabilizing Greek key motifs [106]…”

A novel missense mutation of CRYBB1 causes congenital cataract in a Chinese family

“…Previous studies found that the incidence of AD congenital nuclear cataract is associated with 10 candidate pathogenic genes, including CRYAA, CRYAB, CRYBA1/A3, CRYBB1, CRYGC, CRYGD, CRYGS, GJA3, GJA8, and MIP. [21][22][23][24][25][26][27][28][29][30] The turbid site of congenital nuclear cataract is located in the core of the lens, which can seriously affect the vision of the children, so early detection is particularly important. In the era of precision medicine, the application of PCR technology, Sanger sequencing, next-generation sequencing (NGS), gene editing, and other technologies provide reference for clinically unexplained genetic diseases and then provide molecular basis for prenatal screening, diagnosis, and treatment of genes, to achieve tertiary prevention and intervention of birth defects and improve the quality of birth.…”

Evaluating gap junction variants for a role in pediatric cataract: an overview of the genetic landscape and clinical classification of variants in the GJA3 and GJA8 genes

“…To assess this from a different perspective, we reviewed the proportion of GJA3 and GJA8 variants reported in studies assessing panels of known cataract causing genes in cohorts of patients with pediatric cataracts. We identified 19 such studies that assessed at least 14 cataract-associated genes and at least 18 families or cases, published between 2009 and 2022 [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. On average 15% of the variants identified were in the GJA3 and GJA8 genes, comparable to the 18% reported in the Cat-Map database [13].…”