A Leaky Deep Intronic Splice Variant in Is Associated with Non-Syndromic Retinitis Pigmentosa.

Background: Inherited retinal diseases (IRDs) are clinically complex and genetically heterogeneous visual impairment disorders with varying penetrance and severity. Disease-causing variants in at least 289 nuclear and mitochondrial genes have been implicated in their pathogenesis.

Methods: Whole exome sequencing results were analyzed using established pipelines and the results were further confirmed by Sanger sequencing and minigene splicing assay.

Functional Characterization of Thyroid Peroxidase Missense Variants Causing Thyroid Dyshormonogenesis in Asian Indian Population.

Introduction: Thyroid dyshormonogenesis (TDH) is a subgroup of congenital hypothyroidism with recessive inheritance resulting from disease-causing variants in thyroid hormone biosynthesis pathway genes, like DUOX2, TG, TPO, SLC5A5, SLC26A4, IYD, DUOXA2, and SLC26A7. Thyroid peroxidase (TPO) is a crucial enzyme involved in thyroid hormone biosynthesis and is one of the frequently mutated genes in patients with TDH. The purpose of the study was to describe the in silico and functional characterization of novel variants in TPO gene identified in patients with TDH.

DISP1 deficiency: Monoallelic and biallelic variants cause a spectrum of midline craniofacial malformations.

Purpose: DISP1 encodes a transmembrane protein that regulates the secretion of the morphogen, Sonic hedgehog, a deficiency of which is a major cause of holoprosencephaly (HPE). This disorder covers a spectrum of brain and midline craniofacial malformations. The objective of the present study was to better delineate the clinical phenotypes associated with division transporter dispatched-1 (DISP1) variants.

Monoallelic loss-of-function BMP2 variants result in BMP2-related skeletal dysplasia spectrum.

Purpose: Bone morphogenic proteins (BMPs) regulate gene expression that is related to many critical developmental processes, including osteogenesis for which they are named. In addition, BMP2 is widely expressed in cells of mesenchymal origin, including bone, cartilage, skeletal and cardiac muscle, and adipose tissue. It also participates in neurodevelopment by inducing differentiation of neural stem cells.

Familial monoallelic CYP26B1 truncating variant causes a syndromic craniosynostosis due to haploinsufficiency ?

Autosomal recessive CYP26B1 disorder is characterised by syndromic craniosynostosis of variable severity, and survival ranging from prenatal lethality to survival into adulthood. Here we report on two related individuals of Asian-Indian origin with syndromic craniosynostosis characterised by craniosynostosis, and dysplastic radial heads, caused by monoallelic CYP26B1 likely pathogenic variant NM_019885.4:c.

A novel homozygous synonymous splicing variant in SELENOI gene causes spastic paraplegia 81.

Background: Hereditary spastic paraplegia 81 is a recently identified, rare autosomal recessive disease, caused by biallelic pathogenic variants in the SELENOI gene, with only two families reported to date. The features documented in the two previous affected families include sensorineural deafness, blindness, cleft palate, delayed motor development, regression of motor skills, impaired intellectual development, poor speech and language acquisition, spasticity, hyperreflexia, white matter abnormalities and cerebral and cerebellar atrophy.

Methods: In the present study, we performed exome sequencing analysis in a single family with two affected siblings to identify the genetic cause of complicated hereditary spastic paraplegia.

A new FOXE1 homozygous frameshift variant expands the genotypic and phenotypic spectrum of Bamforth-Lazarus syndrome.

Bamforth-Lazarus syndrome is a rare autosomal recessive disease caused by biallelic loss-of-function variants in the FOXE1 gene. The condition is characterized by congenital hypothyroidism due to thyroid agenesis or thyroid hypoplasia, cleft palate, spiky hair, with or without choanal atresia, and bifid epiglottis. To date, seven pathogenic variants have been reported in the FOXE1 gene causing Bamforth-Lazarus syndrome.

Functional characterization of novel variants in SMPD1 in Indian patients with acid sphingomyelinase deficiency.

Pathogenic variations in SMPD1 lead to acid sphingomyelinase deficiency (ASMD), that is, Niemann-Pick disease (NPD) type A and B (NPA, NPB), which is a recessive lysosomal storage disease. The knowledge of variant spectrum in Indian patients is crucial for early and accurate NPD diagnosis and genetic counseling of families. In this study, we recruited 40 unrelated pediatric patients manifesting symptoms of ASMD and subnormal ASM enzyme activity.