A novel X‐linked intellectual disability ( XLID ) syndrome with moderate intellectual disability and distinguishing craniofacial dysmorphisms had been previously mapped to the Xq26‐q27 interval. On whole exome sequencing in the large family originally reported with this disorder, we identified a 23 bp frameshift deletion in the RNA binding motif protein X‐linked ( RBMX ) gene at Xq26 in the affected males ( n = 7), one carrier female, absent in unaffected males ( n = 2) and in control databases (7800 exomes). The RBMX gene has not been previously causal of human disease. We examined the genic intolerance scores for the coding regions and the non‐coding regions of RBMX ; the findings were indicative of RBMX being relatively intolerant to loss of function variants, a distinctive pattern seen in a subset of XLID genes. Prior expression and animal modeling studies indicate that loss of function of RBMX results in abnormal brain development. Our finding putatively adds a novel gene to the loci associated with XLID and may enable the identification of other individuals affected with this distinctive syndrome.

Chromosome 22q11.2 deletion syndrome (22q11DS) is a common microdeletion syndrome associated with a markedly elevated risk of schizophrenia in adulthood. Cognitive impairments such as a low IQ and deficits in attention and executive function are common in childhood. The catechol O-methyltransferase (COMT) gene maps within the deleted region and is involved in the degradation of dopamine, a neurotransmitter thought to be important in cognition and the development of schizophrenia. Thus, we examined the correlation between neurocognitive deficits and a common polymorphism Val(158)Met in the COMT gene in a cohort of children with 22q11DS. Our results show that children with 22q11DS who have the Met allele have higher IQ and achievement scores and perform better on measures of prefrontal cognition, such as the Continuous Performance Task, as compared with those with the Val allele. These results confirm that the hemizygous COMT Val(158)Met genotype impacts upon cognition in children with 22q11DS.

Chromosome 22q11 deletion syndrome (22q11DS) is associated with elevated rates of schizophrenia and other psychoses in adulthood. Childhood morphologic brain abnormalities are frequently reported, but the significance of these and their relationship to the development of schizophrenia are unclear. We sought to delineate midline neuroanatomical abnormalities in nonpsychotic children with 22q11DS and their age- and sex-matched controls and compare these to those reported in individuals with schizophrenia. On qualitative analysis, we found a high incidence of midline developmental abnormalities (cavum septum pellucidum, or CSP). On quantitative analysis, the total corpus callosum (CC) area was significantly increased in the patient group and among the subregions, the patients had a significantly larger isthmus. These findings of an increased area of the corpus callosum, specifically the isthmus, have not been reported before in individuals with 22q11DS. We also found a relative lack of the age-related increase in the size of the corpus callosum in the children with 22q11DS. There were no differences in cerebellar vermis measurements between the patient and control groups. Our findings are indicative of frequent midline brain anomalies, including dysgenesis of the corpus callosum, in nonpsychotic children with 22q11DS. Although the increased size of the corpus callosum in our 22q11DS patients is in direct contrast to the decrease seen in schizophrenia, the high frequency of structural midline abnormalities in these nonpsychotic children with 22q11DS is similar to that seen in schizophrenia. Further longitudinal studies on these children will help determine which of these structural abnormalities is/are pertinent to the development of psychosis.

Approximately 70% of individuals with chromosome 22q11 deletion syndrome (22q11DS) have congenital heart defects. A host of other vascular problems in these patients, such as tortuous carotid arteries, Raynaud's phenomenon, unexplained hypotension, hypertension, and hypothermia, raise the possibility that there may be abnormal autonomic regulation of the vascular system. So far, however, there has been no formal report of autonomic dysfunction in patients with 22q11 deletion. We present two infants with 22q11DS, who had profound hypotension after uncomplicated surgeries for congenital heart disease. The hypotension was not responsive to vasopressor treatment (and extracorporeal membrane oxygenation in one infant) and resulted in death, due to multiorgan system failure. Obvious causes, such as poor cardiac contractility, prolonged circulatory arrest, neurological abnormality, sepsis and blood loss were excluded. On autopsy, no abnormalities were found that could explain the hypotension. We hypothesize that these infants died of severe hypotension due to abnormal vascular tone and that this is a variable feature in individuals with 22q11 deletion. The autonomic nervous system, which is responsible for the regulation of vasomotor tone, may be variably affected in 22q11DS. This could have implications for the surgical management of patients with 22q11DS. Further studies on this topic would establish or refute the association between 22q11DS and dysautonomia.

LIPE is an intracellular neutral lipase, which is capable of hydrolyzing a variety of esters and plays a key role in the mobilization of fatty acids from diacylglycerols. The objectives of this study were to characterize the genetic polymorphism of bovine LIPE gene and to evaluate the possible association between three SNPs in the coding regions of this gene with the fatty acid composition of meat in a cattle population. Forty-three unrelated animals from different cattle breeds were re-sequenced and 21 SNPs were detected over approximately 2600 bp, five of these SNPs were novel. Three SNPs were selected, on the basis of evolutionary conservation, to perform validation and association studies in a crossbred cattle population. Our results may suggest a possible association of SNP1 with contents of oleic acid and total monounsaturated fatty acids (p < 0.01), and SNP2 and SNP3 with Heneicosylic acid content (p < 0.01), may be helpful to improve the quality of meat and improve health.

Echocardiography has become the method of choice in the diagnosis of a congenital heart defect (CHD) in neonates with Down syndrome. The most compelling argument for diagnosis of CHD in the neonatal period is the need for early surgical intervention (ideally prior to 6 months of age) in those with a complete atrioventricular (AV) canal. We evaluated the efficacy of a combined approach of physical examination (PE) and electrocardiography (ECG) in the detection of CHD in 49 neonates with Down syndrome. Our findings indicate that most hemodynamically significant defects (78%), especially a complete AV canal, can be detected by this approach. Hemodynamically insignificant minor defects, such as a small patent ductus arteriosus (PDA) and a small atrial septal defect (ASD), may be missed. Thus, echocardiography remains the most sensitive way to diagnose CHD. However, given that the combination of PE and ECG detects the majority of complete AV canal defects, it can be used as an alternative approach when echocardiography is not easily accessible, due to geographic or economic constraints. Follow-up after a few weeks of those with normal PE and ECG findings should enable detection of new symptoms and signs and evolving ECG findings that may have been missed in the immediate newborn period. Patients who are judged by PE and ECG to have CHD will need echocardiographic confirmation.

OBJECTIVE: To determine if a maternal serum uE3 value ≥ 5.00 multiples of the median (MoM) is a useful predictor of a poor pregnancy outcome.METHODS: Between 11/1/93 & 6/1/99, 78,575 women underwent 2nd trimester maternal serum screening using alpha fetoprotein (AFP), human chorionic gonadotropin (hCG) and unconjugated estriol (uE3) levels. After eliminating women who had an increased risk for Down syndrome, open neural tube defects, or Trisomy 18 from the study population, 58 women were identified with an uE3 value ≥ 5.00 MoM. Of these 58 women, 28 women were of more advanced gestational age and 5 women were found to be carrying a multiple gestation. Of the remaining 25 women, 11 women with a maternal serum uE3 value a 5.00 MoM had a normal pregnancy and outcome. Four women were lost to follow-up. Ten women were found to have an abnormal outcome. Abnormal outcomes included preterm delivery (≤ 37 weeks gestation) (n=7), fetal demise (n=2), and birth defects noted at delivery (n=1). The 10 women with abnormal outcomes were matched for race, gestation, and date of screening with women who had a normal 2nd trimester maternal serum screen. A relative risk (RR) for pregnancy complications was determined.RESULTS: A maternal serum uE3 value ≥ 5.00 MoM was associated with a poor pregnancy outcome (RR 53.6 [confidence interval 6.2-463] with a p<0.0001).CONCLUSIONS: Although our sample size is small, maternal serum uE3 values ≥ 5.00 MoM in the 2nd trimester appear to be associated with an increased risk for a poor pregnancy outcome. Due to the limited number of cases reported, this association between an uE3 MoM value ≥ 5.00 and poor pregnancy outcome warrants further investigation.

We report a novel X-linked mental retardation (XLMR) syndrome, with characteristic facial dysmorphic features, segregating in a large North Carolina family. Only males are affected, over four generations. Clinical findings in the seven living affected males include a moderate degree of mental retardation (MR), coarse facies, puffy eyelids, narrow palpebral fissures, prominent supraorbital ridges, a bulbous nose, a prominent lower lip, large ears, obesity, and large testicles. Cephalometric measurements suggest that the affected males have a distinctive craniofacial skeletal structure, when compared with normative measures. Obligate-carrier females are unaffected with MR, but the results of cephalometric skeletal analysis suggest craniofacial dysmorphisms intermediate between affected males and normative control individuals. Unaffected male relatives show no clinical or cephalometric resemblance to affected males. The blood-lymphocyte karyotype and the results of DNA analysis for fragile-X syndrome and of other routine investigations are normal. Linkage analysis for polymorphic DNA markers spanning the X chromosome established linkage to Xq26-q27. Maximum LOD scores were obtained at marker DXS1047 (maximum LOD score = 3.1 at recombination fraction 0). By use of haplotype analysis, we have localized the gene for this condition to an 18-cM genetic interval flanked by ATA59C05 and GATA31E08. On the basis of both the clinical phenotype and the mapping data, we were able to exclude other reported XLMR conditions. Therefore, we believe that a unique recessive XLMR syndrome with a distinctive and recognizable phenotype is represented in this family.

We report the detection of a sex chromosome mosaicism (XY/XXY/XYY) by prenatal interphase FISH (fluorescence in situ hybridization) originally identified as a pseudomosaicism involving 47,XXY cells present in a routine 46,XY cytogenetic analysis. After a fetal demise, interphase FISH identified the sex chromosome mosaicism in all tissues examined while cytogenetic analysis revealed only a normal male cell line. After prolonged exposure to colcemid, cytogenetic analysis identified the 47,XXY cell line. This confirmed the presence of the mosaicism and suggested that the abnormal cell line(s) may have been growth disadvantaged. This in turn may have accounted for the intra‐uterine fetal demise. The identification by FISH and the role of growth‐disadvantaged cell lines may provide a unique insight into chromosomally normal fetal demises. Copyright © 1999 John Wiley & Sons, Ltd.

We report on the second case of duplication (4)(q12q13) with microcephaly, mental retardation, and minor facial anomalies. Duplications involving the distal region of chromosome 4q are well described and share common clinical findings. However, phenotypic abnormalities of duplications of the proximal portion of chromosome 4q are relatively unknown. A comparison of the clinical manifestations of our patient and the single published case suggests that the phenotype of this proximal 4q duplication is relatively mild. This study emphasizes the need to perform chromosome analysis in similar mildly affected/nonspecific cases. Am. J. Med. Genet. 86:51–53, 1999. © 1999 Wiley-Liss, Inc.

We describe 2 brothers with cardiomyopathy and hypergonadotropic hypogonadism and conclude that this is the first description of the Najjar syndrome in the United States. The inheritance may be autosomal recessive.