Achondroplasia in diverse Jewish and Arab populations in Israel: clinical and molecular characterization.

BACKGROUND: Achondroplasia is the most frequent form of disproportionate short stature, characterized by rhizomelic shortening of the limbs. This disorder is inherited as an autosomal dominant trait, although most of the cases are sporadic, a result of a de novo mutation. A recurrent glycine to arginine mutation at codon 380 (G380R) in the transmembrane domain of the fibroblast growth factor receptor 3 gene was found to cause achondroplasia among different populations. This is most uncommon in other autosomal dominant genetic diseases. OBJECTIVES: To determine whether this mutation is also common among Jewish patients from diverse ethnic groups and among the Arab population in Israel. METHODS: We examined the G380R mutation (G > A and G > C transition) and the mutation G375C (G > T transition at codon 375) in 31 sporadic patients and in one family diagnosed clinically to have achondroplasia. RESULTS: We found the G > A transition at codon 380 in 30 of our patients and the G > C transition in one patient. We were not able to detect any of the three mutations in two patients with an atypical form of achondroplasia. CONCLUSIONS: Our results further support the unusual observation that nucleotide 1138 of the FGFR3 gene is the most mutable nucleotide discovered to date across different populations.

Predisposition to the fragile X syndrome in Jews of Tunisian descent is due to the absence of AGG interruptions on a rare Mediterranean haplotype.

We have studied the ethnic distribution of the fragile X syndrome in Israel and have found that 36/136 (26.5%) of apparently unrelated pedigrees were of Tunisian Jewish descent. The Tunisian Jews, however, constitute only 2%-3% of the general Israeli population, identifying the first ethnic group significantly (P < .001) predisposed to the development of this disease. Associated with this increase in disease prevalence, we have found an unusually high incidence of FMR1 CGG repeats devoid of AGG interruptions among the normal Tunisian Jewish population (30/150, or 20.0%). Furthermore, the proportion of these alleles beyond the FMR1 CGG repeat instability threshold (>35 repeats) (8/150, or 5.3%) was significantly greater (P < .04) than that proportion found among non-Tunisian Jewish controls in Israel (1/136). Haplotype analysis has indicated that these large uninterrupted CGG repeat alleles are present on a previously unreported (DXS548-FRAXAC1-FRAXAC2) haplotype that accounts for all observed cases of disease among Tunisian Jewish X chromosomes. The high prevalence of disease among Tunisian Jews, we suggest, is due to a founder effect of this rare haplotype, which is completely devoid of AGG interruptions in the Jewish population of Tunisia.

Ambulatory care of febrile infants younger than 2 months of age classified as being at low risk for having serious bacterial infections.

We prospectively examined whether febrile infants younger than 2 months of age who were defined as being at low risk for having bacterial infection could be observed as outpatients without the usual complete evaluation for sepsis and without antibiotic treatment. A total of 237 previously healthy febrile infants were seen at the Pediatric Emergency Room over 17 1/2 months. One hundred forty-eight infants (63%) fulfilled the criteria for being at low risk: no physical findings consisting of soft tissue or skeletal infections, no purulent otitis media, normal urinalysis, less than 25 white blood cells per high-power field on microsopic stool examination, peripheral leukocyte count 5000 to 15,000/mm3 with less than 1500 band cells/mm3. One infant appeared too ill to be included, and had sepsis and meningitis. None of the 148 infants at low risk had bacterial infections, versus 21 of 88 (24%) of those at high risk (P less than 0.0001); eight of 88 (9%) had bacteremia. Of the 148 infants classified as being at low risk for having bacterial infection, 62 (42%) were discharged to home, and 72 (49%) were initially observed for less than or equal to 24 hours and then discharged. Seventeen infants (11%) were hospitalized: in six, low risk became high risk; six had indications other than fever; and five because the study physicians could not be found. The 137 nontreated infants were closely observed as outpatients. The duration of fever was less than 48 hours in 42%, and less than 96 hours in 91%. All infants were observed for at least 10 days after the last examination. The fever resolved spontaneously in all infants but two, with otitis media, who were treated as outpatients. Our data suggest that management of fever in selected young infants as outpatients is feasible if meticulous follow-up is provided.