Mutations in the two ribosomal RNA genes in mitochondrial DNA among Finnish children with hearing impairment.

BACKGROUND: Mutations in the two MT-RNR genes in mitochondrial DNA can cause hearing impairment that presents with variable severity and age of onset. In order to study the prevalence of mutations in MT-RNR1 and MT-RNR2 genes among Finnish children, we studied a ten-year cohort of hearing impaired children born in Northern Finland. METHODS: We studied children, who had been born in Northern Finland in 1993-2002 and who had been ascertained to have hearing impairment by 31 December 2007. Samples from 103 children were sequenced in order to find mutations in the MT-RNR1 and MT-RNR2 genes. RESULTS: One child harboured the pathogenic m.1555A > G mutation in MT-RNR1 suggesting a frequency of 4.4/100,000 in the Finnish paediatric population. In addition, eight rare variants and 13 polymorphisms were found in MT-RNR1 and MT-RNR2 genes. Five of the rare variants were deemed to be haplogroup-specific polymorphisms rather than putative pathogenic mutations, while the remaining three variants have been reported in various haplogroups. Among them m.990 T > C occurs at a conserved site. CONCLUSIONS: The presence of m.990 T > C variant in various haplogroups and the rather high degree of conservation at this site suggest that this transition is a pathogenic rather than homoplasic neutral variant. Identification of further patients with m.990 T > C and segregation analysis in their families should help in determining the pathogenic potential of this variant.

WFS1 mutations in hearing-impaired children.

OBJECTIVE: Mutations in the WFS1 gene can cause Wolfram syndrome or nonsyndromic hearing impairment (HI). The objective of this study was to ascertain the presence of mutations in WFS1 among children with HI from unknown causes. DESIGN: We screened 105 Finnish children with HI for mutations in exon 8 in WFS1. STUDY SAMPLE: Children were born in a defined area in Northern Finland and they had sensorineural, mild to profound, syndromic, or nonsyndromic HI. They were negative for GJB2 mutations and for the m.1555A> G and m.3243A> G mutations in mitochondrial DNA. RESULTS: We found three rare variants and the novel p.Gly831Ser variant in WFS1. Segregation analysis suggested that the novel variant had arisen de novo. The p.Gly831Ser variant may be a new member to the group of heterozygous WFS1 mutations that lead to HI, while the pathogenicity of the rare variant p.Gly674Arg remained unclear. The other two rare variants, p.Glu385Lys and p.Glu776Val, did not segregate with HI in the families. CONCLUSIONS: WFS1 gene mutations are a rare cause of HI among Finnish children with HI.

Audiological follow-up of children with the m.1555A>G mutation in mitochondrial DNA.

The age at onset and the severity of hearing impairment (HI) varies widely among subjects and within families with the m.1555A>G mutation in mitochondrial DNA. We examined prospectively the hearing of 19 children in three nuclear families of a pedigree with m.1555A>G during a period of 7.8 years. The children underwent an audiological examination annually. At the end of the follow-up, the children were 2-13 years old. The parents were asked about the exposure of the children to risk factors of HI. We found that the 19 children with m.1555A>G were born with normal hearing and that 10 of them had developed HI by the end of the follow-up. High frequencies were affected first. The median age at the onset of HI was 3.7 years. Both the severity of HI and the age of onset varied within and between families. Most commonly, audiograms revealed a sensorineural, progressive HI sloping towards high frequencies. We could not identify environmental factors which could modify the development of HI. In conclusion, we were able to pinpoint the time of onset of HI and to follow the progression of HI in childhood. Our results show that there are distinct phenotypes, but at present there are no means to predict which phenotype will develop. It is important to follow up the hearing of children in families with the m.1555A>G mutation, because these children generally pass the newborn hearing screening, and the age at onset or the phenotype of HI cannot be predicted.

[Assistive communication devices improve life management]. / Puhe puuttuu, motoriikka mättää- -kommunikoinnin apuvälineet vahvistavat elämänhallintaa.

The development of information technology has enabled communication for severely disabled persons who previously were isolated even from their immediate neighborhood. Applications of information technology, particularly the Internet, make contacts possible even when spoken communication is impossible. Successful communication will support the personal autonomy of a severely disabled person and also relieves the anxiety of the family members, especially at the final stage of a progressive disease. Thorough elucidation of the user's needs and finding the most appropriate solution for communication and association is essential.

Children with specific language impairment in Finnish: the use of tense and agreement inflections.

Children with specific language impairment (SLI) vary widely in their ability to use tense/agreement inflections depending on the type of language being acquired, a fact that current accounts of SLI have tried to explain. Finnish provides an important test case for these accounts because: (1) verbs in the first and second person permit null subjects whereas verbs in the third person do not; and (2) tense and agreement inflections are agglutinating and thus one type of inflection can appear without the other. Probes were used to compare the verb inflection use of Finnish-speaking children with SLI, and both age-matched and younger typically developing children. The children with SLI were less accurate, and the pattern of their errors did not match predictions based on current accounts of SLI. It appears that children with SLI have difficulty learning complex verb inflection paradigms apart from any problem specific to tense and agreement.

Atypical perceptual narrowing in prematurely born infants is associated with compromised language acquisition at 2 years of age.

BACKGROUND: Early auditory experiences are a prerequisite for speech and language acquisition. In healthy children, phoneme discrimination abilities improve for native and degrade for unfamiliar, socially irrelevant phoneme contrasts between 6 and 12 months of age as the brain tunes itself to, and specializes in the native spoken language. This process is known as perceptual narrowing, and has been found to predict normal native language acquisition. Prematurely born infants are known to be at an elevated risk for later language problems, but it remains unclear whether these problems relate to early perceptual narrowing. To address this question, we investigated early neurophysiological phoneme discrimination abilities and later language skills in prematurely born infants and in healthy, full-term infants. RESULTS: Our follow-up study shows for the first time that perceptual narrowing for non-native phoneme contrasts found in the healthy controls at 12 months was not observed in very prematurely born infants. An electric mismatch response of the brain indicated that whereas full-term infants gradually lost their ability to discriminate non-native phonemes from 6 to 12 months of age, prematurely born infants kept on this ability. Language performance tested at the age of 2 years showed a significant delay in the prematurely born group. Moreover, those infants who did not become specialized in native phonemes at the age of one year, performed worse in the communicative language test (MacArthur Communicative Development Inventories) at the age of two years. Thus, decline in sensitivity to non-native phonemes served as a predictor for further language development. CONCLUSION: Our data suggest that detrimental effects of prematurity on language skills are based on the low degree of specialization to native language early in development. Moreover, delayed or atypical perceptual narrowing was associated with slower language acquisition. The results hence suggest that language problems related to prematurity may partially originate already from this early tuning stage of language acquisition.

Event-related brain potentials to change in the frequency and temporal structure of sounds in typically developing 5-6-year-old children.

The brain's ability to recognize different acoustic cues (e.g., frequency changes in rapid temporal succession) is important for speech perception and thus for successful language development. Here we report on distinct event-related potentials (ERPs) in 5-6-year-old children recorded in a passive oddball paradigm to repeated tone pair stimuli with a frequency change in the second tone in the pair, replicating earlier findings. An occasional insertion of a third tone within the tone pair generated a more merged pattern, which has not been reported previously in 5-6-year-old children. Both types of deviations elicited pre-attentive discriminative mismatch negativity (MMN) and late discriminative negativity (LDN) responses. Temporal principal component analysis (tPCA) showed a similar topographical pattern with fronto-central negativity for MMN and LDN. We also found a previously unreported discriminative response complex (P340-N440) at the temporal electrode sites at about 140 ms and 240 ms after the frequency deviance, which we suggest reflects a discriminative processing of frequency change. The P340 response was positive with a clear radial distribution preceding the fronto-central frequency MMN by about 30 ms. The results indicate that 5-6-year-old children can detect frequency change and the occasional insertion of an additional tone in sound pairs as reflected by MMN and LDN, even with quite short within-stimulus intervals (150 ms and 50 ms). Furthermore, MMN for these changes is preceded by another response to deviancy, temporal P340, which seems to reflect a parallel but earlier discriminatory process.

Connexin 26 mutations and nonsyndromic hearing impairment in northern Finland.

OBJECTIVE: The aims of the present study were to evaluate the role of the gap junction protein beta-2 gene (GJB2), encoding connexin 26 (Cx26), in children with moderate to profound prelingual nonsyndromic sensorineural hearing impairment (HI) and to investigate the carrier frequencies of the GJB2 gene mutations in a control population in Northern Finland. METHODS: Mutation analysis was performed by direct sequencing and carrier detection by conformation sensitive gel electrophoresis further confirmed by direct sequencing. RESULTS: Cx26 mutations were found in 15 of 71 (21.1%) (67 families) children with HI. Homozygosity for the mutation 35delG was shown to be the cause of HI in 13 of 15 (86.7%) children. Homozygosity for the M34T genotype was found in one child, and compound heterozygosity for the M34T/V37I genotype was found in another. Five families of those with suspected familial HI (29.4%) and six families out of those with sporadic HI (12.0%) had a homozygous or compound heterozygous mutation. The carrier frequency for the mutation 35delG was 1 of 78 (4 of 313) and that for the M34T was 1 of 26 (12 of 313). CONCLUSION: 35delG/35delG genotype was found to be a significant cause of moderate to profound prelingual nonsyndromic sensorineural HI in Northern Finland. M34T/M34T genotype was seen in only one child, but the carrier frequency of the M34T allele was about three times higher than that of the 35delG mutation.

Childhood hearing impairment in northern Finland, etiology and additional disabilities.

OBJECTIVES: The purpose of this study was to determine the prevalence and etiology of hearing impairment (HI) in Finnish children and to evaluate the frequency and type of additional disabilities among children with HI. METHODS: Subjects consisted of 214 children with mild to profound HI ascertained until the age of 10 years. They belonged to the birth cohort spanning the years 1993-2002 in northern Finland. The clinical data were collected from the electronic patient records of the Oulu University Hospital. Age at ascertainment, degree and type of HI and audiogram configuration were determined. Risk factors and etiology of HI and co-existing disabilities were recorded. RESULTS: The prevalence of childhood HI was 2.3/1000 live births (95% CI; 2.0, 2.7). The etiology of HI was genetic in 47.2%, acquired in 16.4% and unknown in 36.4% children. Among the 214 children with HI, 101 (47.2%) had other minor or major disabilities. The frequency of additional disabilities did not differ between children with mild HI and those with moderate or severe HI (p=0.78). Additional disabilities were more common (65.7%) in children with acquired HI than in children with genetic or unknown HI (43.6%) (p=0.035). CONCLUSION: The prevalence of childhood HI has remained unchanged in northern Finland as compared to previous studies. Genetic causes were the most common (47%) etiology of childhood HI. Among acquired causes of HI, perinatal risk factors were more common than previously. The frequency of additional disabilities was similar among children with different degrees of HI. Because almost 40% of children had one or more additional disabilities affecting development or learning, it is important to take them into consideration in rehabilitation.

Noun Case Suffix Use by Children with Specific Language Impairment: An Examination of Finnish.

Finnish-speaking children with specific language impairment (SLI, N = 15, M age = 5;2), a group of same-age typically developing peers (TD-A, N = 15, M age = 5;2) and a group of younger typically developing children (TD-Y, N = 15, M age = 3;8) were compared in their use of accusative, partitive, and genitive case noun suffixes. The children with SLI were less accurate than both groups of TD children in case marking, suggesting that their difficulties with agreement extend to grammatical case. However, these children were also less accurate in making the phonological changes in the stem needed for suffixation. This second type of error suggests that problems in morphophonology may constitute a separate problem in Finnish SLI.