Mildred L. Kistenmacher

The association of the DiGeorge anomalad with partial monosomy of chromosome 22

We have seen three unrelated patients with the DiGeorge anomalad who also had the same deletion of chromosome 22 (pter leads to qll). In each, the remaining long arm material (qll leads to qter) was translocated to a different autosome. Our patients and a review of the literature, including a recent report of a family having four infants with the DiGeorge anomalad and the same deletion of chromosome 22 (de la Chapelle et al: Hum Genet 57:253, 1981), make a strong argument for at least some cases of the DiGeorge anomalad arising from a deletion of the pericentromeric region of chromosome 22.

OA1 Mutations and Deletions in X-Linked Ocular Albinism

X-linked ocular albinism (OA1), Nettleship-Falls type, is characterized by decreased ocular pigmentation, foveal hypoplasia, nystagmus, photodysphoria, and reduced visual acuity. Affected males usually demonstrate melanin macroglobules on skin biopsy. We now report results of deletion and mutation screening of the full-length OA1 gene in 29 unrelated North American and Australian X-linked ocular albinism (OA) probands, including five with additional, nonocular phenotypic abnormalities (Schnur et al. 1994). We detected 13 intragenic gene deletions, including 3 of exon 1, 2 of exon 2, 2 of exon 4, and 6 others, which span exons 2-8. Eight new missense mutations were identified, which cluster within exons 1, 2, 3, and 6 in conserved and/or putative transmembrane domains of the protein. There was also a splice acceptor-site mutation, a nonsense mutation, a single base deletion, and a previously reported 17-bp exon 1 deletion. All patients with nonocular phenotypic abnormalities had detectable mutations. In summary, 26 (approximately 90%) of 29 probands had detectable alterations of OA1, thus confirming that OA1 is the major locus for X-linked OA.

Quinacrine fluorescence and Giemsa banding in trisomy 22.

SummaryUsing quinacrine fluorescence and Giemsa banding techniques we have identified an extra chromosome 22 in three non-mongoloid children with similar phenotypes and 47 chromosomes. In one of the children, the long arm of the extra 22 was shorter than usual. This 22q—chrcmcscme was observed in 4 normal family members with 46 chromosomes. In a fourth child, with similar physical findings, the extra G chromosome was shown to be neither a normal 21 nor 22. It must have arisen from a rearrangement in a parental gamete since it was not present in either parents karyotype.No constellation of clinical findings, in association with an extra G chromosome, is sufficient evidence for the diagnosis of trisomy 22. The positive identification of the extra chromosome must be made using fluorescence and banding.

Ocular Histopathologic and Biochemical Studies of the Cerebrohepatorenal Syndrome (Zellweger's Syndrome) and its Relationship to Neonatal Adrenoleukodystrophy

The eyes of three infants with cerebrohepatorenal disease (Zellwegers syndrome) who died demonstrated ganglion cell loss, gliosis of the nerve fiber layer and optic nerve, optic atrophy, and changes resembling those of retinitis pigmentosa in the retina and pigment epithelium. Ultrastructural examination showed bileaflet inclusions identical to those seen in neonatal adrenoleukodystrophy in the pigment epithelium and in pigmented macrophages, but these were absent in the cornea. Biochemical analysis of tissues demonstrated an excessive amount of very-long-chain fatty acids in the ocular tissues, an abnormality also found in adrenoleukodystrophy. These histopathologic and biochemical results demonstrated that the cerebrohepatorenal syndrome and neonatal adrenoleukodystrophy are similar in regard to ocular abnormalities and the presence of saturated very-long-chain fatty acids.

Focal dermal hypoplasia syndrome in a male

Focal dermal hypoplasia (Goltz syndrome) is characterized by a pathognomonic abnormality of the skin in association with other congenital defects. There are only seven males among the 52 reported cases. We report the eighth case in a male and evaluate the possible genetic origin of the syndrome. A critical review of the literature provides no evidence for the previously accepted single gene mode of inheritance.

539 PRESUMPTIVE EVIDENCE FOR THE PRESENCE OF 2 ACTIVE X CHROMOSOMES IN A BALANCED X-AUTOSOLL TRANSLOCATION

In human somatic cells, X chromosomes in excess of one are late replicating. In balanced X-autosome translocation, the general rule is that the normal X is late replicating. We are reporting the first such translocation in which there is no late replicating X in 1/3 of cells analyzed. A 6-year-old girl with the Beckwith-Wiedemann syndrome has a balanced, de novo, X;1 translocation (G-banded karyotype is 46,X,t(X;1) (Xpter→ Xq26::1q12→ lqter; lpter→ 1q12::Xq26→ Xqter). Using the BrdU terminal pulse method followed by acridine orange or Hoechst 33258 stain and giemsa in 2 successive lymphocyte cultures, the normal X was identified as late replicating in approximately 66% of metaphases. In the remaining 34% of cells, neither the normal X nor the Xt appeared to be late replicating. In these cells, regions of chromosomes 4 and 13, known to be late replicating, are clearly identifiable. In no case did the small Xq portion in the reciprocal translocation chromosome appear as late replicating. This finding serves as presumptive evidence for the presence of 2 active X chromosomes in a balanced X-autosome translocation.Supported in part by NIH grants # RR75 and CA 19834

914 ASSOCIATION OF CHROMOSOME ABNORMALITIES WITH FETAL DILANTIN SYNDROME

The Fetal Dilantin Syndrome (FDS) is a clinical entity of recognizable congenital defects associated with maternal exposure to Dilantin, either alone or with other anticonvulsant medications. We have recently investigated four patients with FDS. Two of these patients had coexistent chromosomal abnormalities, Klinefelter syndrome and a 14/21 translocation respectively. In addition to the typical findings of FDS, both had defects not usually associated with the syndrome. There was one previous patient described who had coexistent Turner syndrome and FDS by Chen, et. al. (Birth defects: Original Article Series XIII (3B) : 237-8, 1977). Patients with FDS should be karyotyped, especially if atypical clinical findings are present.Supported in part by NIH Grant CA 19834