Genetic studies on speech and language disorders / 동물의과학연구지

Speech and language are uniquely human-specific traits that have contributed to humans becoming the predominant species on earth from an evolutionary perspective. Disruptions in human speech and language function may result in diverse disorders, including stuttering, aphasia, articulation disorder, spasmodic dysphonia, verbal dyspraxia, dyslexia, and specific language impairment (SLI). These disorders often cluster within a family, and this clustering strongly supports the hypothesis that genes are involved in human speech and language functions. For several decades, multiple genetic studies, including linkage analysis and genomewide association studies, were performed in an effort to link a causative gene to each of these disorders, and several genetic studies revealed associations between mutations in specific genes and disorders such as stuttering, verbal dyspraxia, and SLI. One notable genetic discovery came from studies on stuttering in consanguineous Pakistani families; these studies suggested that mutations in lysosomal enzyme-targeting pathway genes (GNPTAB, GNPTG, and NAPGA) are associated with non-syndromic persistent stuttering. Another successful study identified FOXP2 in a Caucasian family affected by verbal dyspraxia. Furthermore, an abnormal ultrasonic vocalization pattern (USV) was observed in knock-in (KI) and humanized mouse models carrying mutations in the FOXP2 gene. Although studies have increased our understanding of the genetic causes of speech and language disorders, these genes can only explain a small fraction of all disorders in patients. In this paper, we summarize recent advances and future challenges in an effort to reveal the genetic causes of speech and language disorders in animal models.

Recent advances in genetic studies of stuttering

Speech and language are uniquely human-specific traits, which contributed to humans becoming the predominant species on earth. Disruptions in the human speech and language function may result in diverse disorders. These include stuttering, aphasia, articulation disorder, spasmodic dysphonia, verbal dyspraxia, dyslexia and specific language impairment. Among these disorders, stuttering is the most common speech disorder characterized by disruptions in the normal flow of speech. Twin, adoption, and family studies have suggested that genetic factors are involved in susceptibility to stuttering. For several decades, multiple genetic studies including linkage analysis were performed to connect causative gene to stuttering, and several genetic studies have revealed the association of specific gene mutation with stuttering. One notable genetic discovery came from the genetic studies in the consanguineous Pakistani families. These studies suggested that mutations in the lysosomal enzyme-targeting pathway genes (GNPTAB, GNPTG and NAPGA) are associated with non-syndromic persistent stuttering. Although these studies have revealed some clues in understanding the genetic causes of stuttering, only a small fraction of patients are affected by these genes. In this study, we summarize recent advances and future challenges in an effort to understand genetic causes underlying stuttering.

A case of mucolipidosis II presenting with prenatal skeletal dysplasia and severe secondary hyperparathyroidism at birth / 소아과

Mucolipidosis II (ML II) or inclusion cell disease (I-cell disease) is a rarely occurring autosomal recessive lysosomal enzyme-targeting disease. This disease is usually found to occur in individuals aged between 6 and 12 months, with a clinical phenotype resembling that of Hurler syndrome and radiological findings resembling those of dysostosis multiplex. However, we encountered a rare case of an infant with ML II who presented with prenatal skeletal dysplasia and typical clinical features of severe secondary hyperparathyroidism at birth. A female infant was born at 37(+1) weeks of gestation with a birth weight of 1,690 g (T (p.Arg1031X) and c.3456_3459dupCAAC (p.Ile1154GlnfsX3), the latter being a novel mutation. The infant was treated with vitamin D supplements but expired because of asphyxia at the age of 2 months.