Atsuko Fujimoto

Direct duplication of 9p22→p24 in a child with duplication 9p syndrome

A de novo direct duplication of 9p22-->p24 was shown in a child with a duplication 9p phenotype by GTG banding and fluorescence in situ hybridization (FISH) using a chromosome-9 specific painting probe as well as 6 YAC DNA probes localized to the 9p13-9p23 region. The breakpoints in this patient and previously reported patients suggest that 9p22 may be the critical region for duplication 9p syndrome.

Inherited partial duplication of chromosome No. 15

A boy with unusual facial appearance and mental retardation was found to have duplication for the distal half of the long arm of chromosome No. 15 and possibly deficiency for the distal end of the long arm of No. 21. The chromosome abnormality was inherited from his mother, who had a translocation involving chromosomes Nos. 15 and 21. Giemsa-banding localized the break point in chromosome No. 15 just distal to the intense band at the midportion of the long arm. The break point in chromosome No. 21 appeared to be at the distal end of the long arm. The difficulty encountered in cytogenetic analysis of the propositus with conventional staining, the importance of chromosome analysis of the parents, and the application of differential staining techniques are also presented.

Clinical, morphological, and biochemical phenotype of a new case of Ehlers‐Danlos syndrome type VIIC

Ehlers-Danlos syndrome (EDS) type VIIC is a newly recognized human disorder which results from failure to remove the amino-terminal propeptide of type I procollagen. Four cases of EDS type VIIC have been reported, and here we describe a fifth case. The propositus was a 1,445 g male infant born at 30 weeks of gestation following premature rupture of membranes. He had wide fontanelles, prominent eyes with swollen eyelids and blue sclerae, anteverted nostrils, micrognathia, umbilical hernia, short stubby fingers, and cutis laxa with hirsutism. At age 3 months, during the repair of the umbilical hernia, he was noted to have unusual skin fragility. Examination of skin by scanning electron microscopy showed frayed collagen fibrils, and transmission electron microscopy showed the hieroglyphic collagen fibril morphology characteristic of the disorder. As reported in other cases, cultured fibroblasts synthesized type I procollagen that was very poorly processed at the amino-terminal propeptide cleavage site. the 5 known cases of human EDS type VIIC characterize a distinct clinical phenotype, making this condition recognizable at birth before manifestation of severe skin fragility. The diagnosis can be confirmed by biochemical studies of type I procollagen synthesis and by electron microscopic examination of skin.

Giant satellites or translocation

An infant with craniostenosis and retardation was found to have giant satellites on chromosome No. 13. Trypsin-Giemsa banding studies demonstrated, in addition, a partially deleted short arm of chromo

Two alpha-glucosidases in cultured amniotic fluid cells and their differentiation in the prenatal diagnosis of Pompe's disease.

A sensitive fluorometric assay utilizing 4-methylumbelliferyl-alpha-D-glucopyranoside has been developed for the determination of alpha-glucosidase. The enhanced sensitivity was achieved by increasing the solubility of the substrate with a water miscible organic solvent. With this system, cultured amniotic fluid cells were found to have two major forms of alpha-glucosidase with somewhat overlapping acidic pH optima; one with pH optimum at 4.5 is deficient in Pompes disease (type II glycogenosis), while one with pH optimum at 6.0 is not affected in this disease. Specificity for the pH 4 form of alpha-glucosidase was achieved by exploiting the greater thermal lability of the pH 6 enzyme. The pH 6 form of the enzyme was also detectable in freshly prepared extracts of cultured fibroblasts. The procedure is direct and simple and has been applied to the prenatal diagnosis in two pregnancies at risk for Pompes disease.

Trisomy 13 in Two Infants with Cyclops

Two infants with cyclops malformation were born at the University of Southern California Medical Center during the past three years. The karyotypes of both infants demonstrated an extra chromosome No. 13: one with 47,XX,+13 and one with 46,XX,-14,+t(13q14q). The physical findings, karyotypes with trypsin-Giemsa banding, and association of trisomy 13 syndrome with cyclops malformation are presented.

A Fetus With Recombinant of Chromosome 8 Inherited From her Carrier Father

SummaryA pericentric inversion of chromosome 8, inv(8)(p23q22), in a male carrier resulted in an unbalanced recombinant, rec(8)dup q, inv(8)(p23q22), which was diagnosed prenatally. The features seen in the aborted fetus resembled the features seen in a previously affected child who received the identical recombinant from her carrier mother. In this particular inversion involving chromosome 8, both male and female carriers risk producing an unbalanced progeny. Different familial pericentric inversions are reviewed for the presence or absence of unbalanced recombinants.

Double Autosomal Trisomy and Mosaicism for Chromosomes No. 8 and No. 21

This patient was found to have a previously unreported double trisomy for chromosomes No. 8 and No. 21. She was recognized to have Downs syndrome at birth, and her subsequent development was consistent with that diagnosis. Her general health was good and there were no features suggesting an additional chromosomal abnormality. At this time there is no clearly recognized phenotype associated with trisomy 8. Two non-disjunctional events, occurring in meiosis and/or post-zygotic mitosis, are possible explanations of the chromosomal abnormalities found in this patient.

Duplication of the segment q12.2→qter of chromosome 22 due to paternal inversion 22(p13q12.2)

SummaryA 1730-g male infant, born at 37 weeks gestation, had multiple congenital anomalies, consisting of microcephaly, hypertelorism, bilateral cleft lip and palate, micrognathia, lowset ears, and cryptorchidism. Chromosome analysis showed a recombinant 22 derived from the paternal inversion (22) (p13q12.2). The probands karyotype is 46,XY,rec(22),dup q,inv(22)(p13q12.2)pat, which has a duplication of q12.2→qter. An identical recombinant has been reported in a female infant in Mexico whose mother was a carrier of the inversion. Similar congenital anomalies present in these two patients demonstrate the phenotype of duplication of the distal long arm 22. This report also documents the occurrence of an identical inversion in two apparently unrelated Mexican families.

Relative inability of mother and child to convert phenylalanine to tryosine—A possible cause of nonspecific mental retardation☆

Abstract In order to test the hypothesis that hereditary deficiencies in nonessential amino acid synthesis might be an important basis of mental retardation, we looked for associated heterozygosity for phenyketonuria in mother-child pairs among 18 families with nonspecific mental retardation. Although no evidence of phenylketonuria exists in any of these families, 6 showed such association. This represents approximately 30 times chance association and suggests that heterozygosity for phenylketonuria may play a major role in the prenatal development of nonspecific mental retardation.