Browsing by Author "Kishnani, Priya"

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Open Access
Auditory-Perceptual Speech Features in Children With Down Syndrome.
(American journal on intellectual and developmental disabilities, 2019-07) Jones, Harrison N; Crisp, Kelly D; Kuchibhatla, Maragatha; Mahler, Leslie; Risoli, Thomas; Jones, Carlee W; Kishnani, Priya
Speech disorders occur commonly in individuals with Down syndrome (DS), although data regarding the auditory-perceptual speech features are limited. This descriptive study assessed 47 perceptual speech features during connected speech samples in 26 children with DS. The most severely affected speech features were: naturalness, imprecise consonants, hyponasality, speech rate, inappropriate silences, irregular vowels, prolonged intervals, overall loudness level, pitch level, aberrant oropharyngeal resonance, hoarse voice, reduced stress, and prolonged phonemes. These findings suggest that speech disorders in DS are due to distributed impairments involving voice, speech sound production, fluency, resonance, and prosody. These data contribute to the development of a profile of impairments in speakers with DS to guide future research and inform clinical assessment and treatment.
Open Access
DOWN SYNDROME
(2021-02-19) Korlimarla, Aditi; Hart, Sarah; Spiridigliozzi, Gail; Kishnani, Priya
Down syndrome is the most common identifiable genetic cause of intellectual disability. The facial appearance of individuals with Down syndrome is highly characteristic and is frequently associated with other minor anomalies and malformations of other body systems, most importantly the cardiovascular and gastrointestinal systems. Individuals with Down syndrome also have an increased likelihood of a number of medical complications including those of the thyroid gland, and the gastrointestinal, upper‐respiratory, audiologic, hematological, and neurological systems. It is thus important for persons with Down syndrome to be followed in a systematic fashion and have access to appropriate specialists to anticipate, prevent, or modify potential complications. Current research continues to shed light on many behavioral and medical aspects of Down syndrome, but questions remain about the relationship between the trisomy of chromosome 21, the developmental and behavioral pattern, and the health complications.
Open Access
Pathogenesis of growth failure and partial reversal with gene therapy in murine and canine Glycogen Storage Disease type Ia.
(Molecular Genetics and Metabolism, 2013-06) Brooks, Elizabeth Drake; Little, Dianne; Arumugam, Ramamani; Sun, Baodong; Curtis, Sarah; Demaster, Amanda; Maranzano, Michael; Jackson, Mark W; Kishnani, Priya; Freemark, Michael S; Koeberl, Dwight D
Glycogen Storage Disease type Ia (GSD-Ia) in humans frequently causes delayed bone maturation, decrease in final adult height, and decreased growth velocity. This study evaluates the pathogenesis of growth failure and the effect of gene therapy on growth in GSD-Ia affected dogs and mice. Here we found that homozygous G6pase (-/-) mice with GSD-Ia have normal growth hormone (GH) levels in response to hypoglycemia, decreased insulin-like growth factor (IGF) 1 levels, and attenuated weight gain following administration of GH. Expression of hepatic GH receptor and IGF 1 mRNAs and hepatic STAT5 (phospho Y694) protein levels are reduced prior to and after GH administration, indicating GH resistance. However, restoration of G6Pase expression in the liver by treatment with adeno-associated virus 8 pseudotyped vector expressing G6Pase (AAV2/8-G6Pase) corrected body weight, but failed to normalize plasma IGF 1 in G6pase (-/-) mice. Untreated G6pase (-/-) mice also demonstrated severe delay of growth plate ossification at 12 days of age; those treated with AAV2/8-G6Pase at 14 days of age demonstrated skeletal dysplasia and limb shortening when analyzed radiographically at 6 months of age, in spite of apparent metabolic correction. Moreover, gene therapy with AAV2/9-G6Pase only partially corrected growth in GSD-Ia affected dogs as detected by weight and bone measurements and serum IGF 1 concentrations were persistently low in treated dogs. We also found that heterozygous GSD-Ia carrier dogs had decreased serum IGF 1, adult body weights and bone dimensions compared to wild-type littermates. In sum, these findings suggest that growth failure in GSD-Ia results, at least in part, from hepatic GH resistance. In addition, gene therapy improved growth in addition to promoting long-term survival in dogs and mice with GSD-Ia.