With this sixth edition, the publishers have faced a number of challenges. The explosive growth of knowledge in the broad fields covered by this monumental work has forced expansion to two volumes. Four younger editors have coordinated the efforts of 218 contributors, while the three senior editors from the previous editions serve, in the interest of preserving some continuity, as consulting editors. Of course, many of the chapters benefit from having at least some of the same writers. It seems that all have wisely approached their tasks with a blend of freshness and due regard for a classic that soon enters its fourth decade of reliable service. The first edition appeared in 1960, while I was in college studying zoology. Later, in medical school and fellowship, I was impressed with the early editions as they focused on a variety of concerns that were united by the early genetic investigations. How

The Metabolic Basis of Inherited Disease

Fusidic acid pharmacology, pharmacokinetics and pharmacodynamics.

In five families with questionable chromosome rearrangements, we identified an interchromosomal insertion by fluorescent in situ hybridization (FISH). In case 1 with a dir ins (5;11)(p14;q14q24) in three generations, the mentally retarded and microcephalic proband showed a 5p14-->pter deletion. In case 2, a duplication (13)(q21.31--> q31.2) combined with a deletion (11)(q14-->q22) segregated from a reciprocal ins(11;13)(q14q122)(q21.32q31.2), causing a mixed phenotype with psychomotor retardation, caput quadratum, choanal atresia, and pes equinovarus. In case 3, a dir ins (18;5)(q21.3;p13.1p14) was associated with spontaneous abortions, in case 4, the proband with mental retardation, microcephaly, and a heart defect showed a pure trisomy of (12)(q13-->q15), which had segregated from a carrier of an ins (18;12)(p11.3;q13q15). In case 5, a duplication of (10)(q26.3-->q25.2) segregated from an inv ins(5;10)(q15;q26.3q25.2), which was passed on directly from a mother to her son,with mental retardation. In all families the elucidation of the insertional translocation (IT) considerably increased the associated genetic risks of carriers. For the review, we collected data from 81 articles on 87 IT probands on ascertainment, origin, familial transmittance, progeny, and genetic risks of IT carriers. We also discussed the recombinant chromosomes and complex rearrangements associated with ITs, and listed chromosome regions occurring solely as deletions, or solely as duplications, or as both to facilitate genotype/phenotype correlations. We conclude that ITs are rare chromosomal rearrangements with an 1:80,000 incidence, of which nearly 80% were referred because of congenital abnormalities and mental retardation. A maternal origin was seen in 59.5%, a paternal origin in 26.6%, and 13.9% were de novo. No notable difference in fertility between male and female IT carriers was noticed. Bias of ascertainment was excluded in 15 familial cases and led to an estimate of the genetic risks for IT carriers of 32.0-36.0%. The mean size of the inserted regions occurring solely as duplications (n=39) measures 0.96% of the haploid autosomal length (HAL), and of regions solely occurring as deletions (n=14) 0.47% HAL. In the families where both aneusomies occurred, the size of the insertions ranged between 0.22 and 1.21% HAL. Overall, the findings fit with the general idea that a surplus of genetic material is tolerated more easily than a deficiency.

Interchromosomal insertions. Identification of five cases and a review.

Clinical and chromosomal studies of the 18q-syndrome

A family of three generations has been described with an insertional type of chromosome rearrangement involving chromosomes 11 and 18[46,XX or XY, ins(11;18)(p15;q11q21)] detected by G-banding using a trypsin digestion method. Four members of this family with clinical features of 18q− have inherited the der(18) from their father and are thus deficient for (18)(q11q21). Three other family members have inherited the der(11) and thus have a duplication of the same segment [(18)(q11q21)]. Genetic marker studies on this family, show no significant segregation of any of the markers studied with either the der(11) or der(18). Eight family members had the PepA8PepA1 genotype and four of these were carrying the der(18), indicating that the PepA locus which had been previously assigned to chromosome 18, does not lie in the segment q11→q21.

https://jmg.bmj.com/content/jmedgenet/11/4/353.full.pdf

Familial mental retardation in a family with an inherited chromosome rearrangement

IgA and partial deletions of chromosome 18

Cytogenetic studies in a 2-year-old boy referred to our laboratory for developmental delay showed an unusual karyotype with a three break rearrangement. R and G banding were both necessary to determine the exact nature of the rearrangement which is described as 46, XY,inv ins(16;3)(q22;p26p13). Several features coincide with the reported description of another patient where 3p26 was missing, and the coincidence is explained as a position effect.

https://jmg.bmj.com/content/jmedgenet/19/2/148.full.pdf

A case of inverted insertion assessed by R and G banding

Clinical, dermatoglyphic and cytogenetic features of a child with apparently balanced karyotype carrying a presumptive 2/E translocation are presented. The relevance of the karyotypic anomaly to the clinical findings is briefly discussed.

Congenital abnormalities in a child with presumptive karyotype 46. XX, t (2q-; 17q+).

Non-specific X-linked mental retardation with fragile X chromosome: somatic features, cytogenetic diagnosis and elements for genetic counselling.

Evaluation of a modified Leighton tube/coverslip technique for skin fibroblast culture has shown its superiority over plasma clot techniques with respect to both simplicity and rapidity. Reference is made to the diagnostic value of this technique for chromosome abnormalities and inborn errors of metabolism.

Joseph Masterson

Papers

IgA and partial deletions of chromosome 18

A case of inverted insertion assessed by R and G banding

Congenital abnormalities in a child with presumptive karyotype 46. XX, t (2q-; 17q+).

Non-specific X-linked mental retardation with fragile X chromosome: somatic features, cytogenetic diagnosis and elements for genetic counselling.

Diagnostic skin fibroblast culture.