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Congenital cataract (CC) is clinically and genetically highly heterogeneous. Here, we enrolled a consanguineous kindred (LUCC15) from Pakistan, with 3 affected individuals suffering with CC. Exome sequencing revealed a transition mutation [c.149 T > C; p.(Ile50Thr)] in INPP5K. Inositol polyphosphate-5-phosphatase K, encoded by INPP5K, is involved in dephosphorylation of phosphatidylinositol (PtdIns) 4,5-bisphosphate, and PtdIns 3,4,5-trisphosphate. Recently, pathogenic variants in INPP5K have been reported in families with congenital muscular dystrophies, intellectual disability, and cataract. In our family LUCC15, mild to moderate intellectual disability along with speech impairment was observed in 2 affected individuals. Magnetic resonance imaging of brain and muscles tissues did not reveal any cerebellar or muscular atrophy. However, electromyography of both upper and lower limbs revealed irritable myopathy. Comparison of clinical phenotype of all the known affected individuals, including LUCC15 family, homozygous for INPP5K alleles revealed reduced penetrance of muscular dystrophy and intellectual disability. Similarly, skeletal muscle abnormalities were highly variable among inpp5ka zebrafish mutants analyzed in this study. These phenotypic variabilities may be due to epigenetic factors and/or genetic modifiers.

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Skeletal dysplasias are highly heterogeneous disorders composed of 40 clinical subtypes that are part of 456 well-delineated syndromes in humans. Here, we enrolled consanguineous kindred from a remote area of Sindh province of Pakistan, with fourteen affected individuals suffering with short stature, kyphoscoliosis, joint dislocations, clubfoot, heart valve anomalies and progressive bilateral mixed hearing loss. To identify pathogenic variants in this family, whole exome sequencing (WES) was performed in one affected and one normal individual, which revealed a novel transversion mutation (c.802G>T; p.Glu268*) in CHST3 associated with the phenotype. CHST3 encodes a chondroitin 6-O-sulfotransferase-1 (C6ST-1) enzyme that is essential for the sulfation of proteoglycans found in cartilages. Previously, mutations in CHST3 have largely been reported in sporadic cases of skeletal dysplasia, primarily with severe spinal abnormalities, joint dislocations, joint contractures, and clubfoot. Clinical and radiological examination of the affected individuals in this family provides new insights into phenotypic spectrum of CHST3 alleles and disease progression with age.

Stuttering is a speech disorder during which the flow of speech is interrupted by involuntary pauses and repetition of sounds. Stuttering identification is an interesting interdisciplinary domain research problem which involves pathology, psychology, acoustics, and signal processing that makes it hard and complicated to detect. Recent developments in machine and deep learning have dramatically revolutionized speech domain, however minimal attention has been given to stuttering identification. This work fills the gap by trying to bring researchers together from interdisciplinary fields. In this paper, we review comprehensively acoustic features, statistical and deep learning based stuttering/disfluency classification methods. We also present several challenges and possible future directions.