Karl-Henrik Gustavson

Frequency of the fragile X syndrome in infantile autism

In a Swedish multicenter study, 102 cases of infantile autism (I.A.) were examined for fragile X (q27). The fragile X syndrome was observed in 13 of the 83 (16%) boys with I.A., but in none of the 19 girls with I.A.

Loss of ZDHHC15 expression in a woman with a balanced translocation t(X;15)(q13.3;cen) and severe mental retardation.

X-linked mental retardation (XLMR) affects one in 600 males and is highly heterogeneous. We describe here a 29-year-old woman with severe nonsyndromic mental retardation and a balanced reciprocal translocation between chromosomes X and 15 [46,XX,t(X;15)(q13.3;cen)]. Methylation studies showed a 100% skewed X-inactivation in patient-derived lymphocytes indicating that the normal chromosome X is retained inactive. Physical mapping of the breakpoints localised the Xq13.3 breakpoint to within 3.9 kb of the first exon of the ZDHHC15 gene encoding a zinc-finger and a DHHC domain containing product. Expression analysis revealed that different transcript variants of the gene are expressed in brain. ZDHHC15-specific RT-PCR analysis on lymphocytes from the patient revealed an absence of ZDHHC15 transcript variants, detected in control samples. We suggest that the absence of the ZDHHC15 transcripts in this patient contributes to her phenotype, and that the gene is a strong candidate for nonsyndromic XLMR.

Fragile site X chromosomes and X-linked mental retardation in severely retarded boys in a northern Swedish county. A prevalence study

In an unselected series of 96 severely mentally retarded boys (IQ < 50) born 1959–70 in a northern Swedish county, six had a fragile site on the distal end of the X chromosome (FraXq 28). The prevalence of the fragile X syndrome in severely retarded boys was 6 %. Next to trisomy 21, this fragile X syndrome appears to be the most common single cause of severe mental retardation in boys.

Fragile X syndrome in mildly mentally retarded children in a northern swedish county. A prevalence study

In an extensive etiological study of an unselected series of mildly mentally retarded children (MMR) (IQ 50–70) born 1959–1970 in a northern Swedish county, 5 of 110 boys (4.5%) and none of 61 girls had a fragile site on the distal end of the X‐chromosome (Fra Xq 28). Consequently fragile X was seen in 2.9% of the total series of 171 children. In a combined series of severe and mild mental retardation, the incidence of the fragile X syndrome was calculated to be 1:3000 in the county of Vasterbotten. Next to trisomy 21 the fragile X syndrome was the most common single identified cause of MMR in boys. A cytogenetic investigation using special cultural conditions and banding techniques should be performed in cases of mental retardation of unclear etiology and in possible female carriers.

The gene for Best's macular dystrophy is located at 11q13 in a Swedish family

A large Swedish family with more than 250 cases of Bests macular dystrophy has been clinically and genetically studied. The gene was traced to a couple born in central Sweden in the 17th century. Highly significant evidence for genetic linkage to DNA markers on chromosome 11q13 was detected. A lod score of 15.12 was obtained at recombination fraction 0.01 with DNA marker INT2 (also called FGF3). The retinally expressed gene ROM1, which maps to the same chromosomal region is a candidate for this genetic disease.

IDENTICAL SYNDROMES OF CEREBRAL PALSY IN THE SAME FAMILY

Familial cases of cerebral palsy were traced all over Sweden. Fortythree families were collected, in 30 of which the patients were siblings. The families were divided into three groups: (1) 16 families with cases of identical syndromes and a history of normal pregnancy, delivery and perinatal period; (2) 3 families with cases of identical syndromes but an abnormal perinatal period; (3) 24 families with non‐identical syndromes.

Relative effect of parental birth weight on infant birth weight at term.

The relations between some hereditary and environmental factors and the variation in infant birth weight were estimated by multiple linear regression analyses on a sample of 276 Scandinavian single term pregnancies.

A Case of XXXXY Sex Chromosome Anomaly with Autoradiographic Studies

A 21-month-old boy with multiple congenital anomalies was found to have 49 chromosomes with an XXXXY sex chromosome constitution. He was mentally retarded with skeletal abnormalities, hypertelorism, m

Prevalence and aetiology of congenital birth defects, infant mortality and mental retardation in Lahore, Pakistan: a prospective cohort study.

AIM To study the health and development of children in a developing and low-income country. METHODS The health and development of children in Lahore in northern Pakistan have been studied since 1981 in a collaborative project between Pakistani and Swedish university institutions and the Swedish Agency for Research Cooperation with Developing Countries (SAREC). The study described in this paper comprised four different areas in Lahore with different degrees of urbanization and different social conditions. All pregnancies in the four areas were registered during the period March 1984 to July 1986 and were followed up from the 5th month of pregnancy. All 1476 children born after 1 September 1984 were followed up from birth to 12 y of age. RESULTS The perinatal mortality in the whole material was 5.4%. It was highest in the periurban slum (7.5%) and lowest in the upper-middle class cohort (3.3%). Overall infant mortality was 10%. It was highest (14%) in the periurban slum and lowest (2%) in the upper-middle class group. Overall incidence of serious birth defects was 5%. It was highest in the periurban slum community (7%) and lowest in the upper-middle class cohort (3%). The overall cumulative incidence of severe mental retardation per 100 live births was 1.1. It was highest (2.2) in the periurban slum and lowest (0.4) in the upper-middle class group. The overall prevalence of mild mental retardation among 6-10-y-old children was 6.2 per 100. It was highest in the periurban slum (10.5) and lowest (1.3 per 100) in the upper-middle class group. Poverty, malnutrition, birth trauma and consanguinity were common causes of infant mortality and mental retardation in Lahore, Pakistan. CONCLUSION Preventive measures with provision of obstetric and health services, services for genetic information and risk evaluation, vaccination programmes and identification of children with retarded development for specific stimulation and habilitation measures, e.g. organized play activities, are important in developing and low-income countries.

A 4-5/21-22 CHROMOSOMAL TRANSLOCATION ASSOCIATED WITH MULTIPLE CONGENITAL ANOMALIES.

I n addition to trisomy 21 (mongolism or Down’s syndrome) with its rather typical manifestations, two less common autosoma1 trisomic syndromes are now recognized. These two involve trisomy of chromosome 17 or 18 [lo] and trisomy of one of the chromosomes in the 13-15 group [22]. Also, mongolism has been observed in some patients to be associated with a total number of 46 chromosomes and a translocation between an extra no. 21 and another chromosome [l, 6, 12, 15, 17, 24, 251. Each of these chromosomal aberrations seems to interfere in a serious and specific manner with development, and the patients usually present a rather characteristic combination of malformations. The present case is that of an infant who has multiple congenital anomalies, including hypotonia, retarded growth and development, marked hydrocephalus, lowset malformed ears, micrognathia, macro-