Jun-Ichi Nagaishi | PubMed Health

PubMed2006

Lower brainstem dysfunction in an infant with persistent primitive trigeminal artery.

A 6-month-old boy with persistent primitive trigeminal artery (PPTA) presented with stridor, dysphagia, delayed motor development and postural neck and shoulder dystonia. Magnetic resonance imaging/angiography and ultrasonography revealed PPTA, with flow from the dilated basilar artery to the right internal carotid artery, lower brainstem compression by the dilated basilar artery, and cerebellar vermis hypoplasia. Evoked potentials showed lower pons and medulla oblongata functional disruption. These lesions may be related to vascular etiology in the lower brainstem or to congenital malformation syndrome involving infratentorial structures. The relationship of this condition to Möbius syndrome is discussed.

Abnormalities, Multiple↗

PubMed2005

Mutation at cleavage site of insulin-like growth factor receptor in a short-stature child born with intrauterine growth retardation.

CONTEXT: Mouse knockout models have clearly demonstrated the critical importance of IGF-I and IGF receptor type 1 (IGF-IR) for embryonic growth as well as postnatal growth. OBJECTIVE: We hypothesized that mutations of IGF-IR gene might predispose to short stature in children born with intrauterine growth retardation (IUGR). PATIENTS: Twenty-four children with unexplained IUGR (birth weight < -1.5 SD) and short stature (<-2.0 SD) were screened for abnormalities of the IGF-IR gene. METHODS: Direct DNA sequencing was used to identify IGF-IR gene mutations. Unprocessed IGF-IR proreceptor in fibroblasts was detected by immunoblot analysis. Functions of mutated IGF-IR in fibroblasts were evaluated by IGF-I binding, and IGF-I-stimulated DNA synthesis and beta-subunit autophosphorylation. RESULTS: We found the following results: 1) a heterozygous mutation (R709Q) changing the cleavage site from Arg-Lys-Arg-Arg to Arg-Lys-Gln-Arg was identified in a 6-yr-old Japanese girl (case 1) and her mother who also had IUGR with short stature (case 2); 2) fibroblasts from case 2 contained more IGF-IR proreceptor protein (189 +/- 26% of normal) and less mature beta-subunit protein (63 +/- 12%); 3) [125I]IGF-I binding to fibroblasts from case 2 was reduced, compared with normal control (0.61 +/- 0.16 x 10(6) vs. 1.14 +/- 0.12 x 10(6) sites per cell; P < 0.05); and 4) both IGF-I-stimulated [3H]thymidine incorporation and IGF-IR beta-subunit autophosphorylation were low in fibroblasts from case 2, compared with those of control (P < 0.05). CONCLUSIONS: These findings strongly suggest that this mutation leads to failure of processing of the IGF-IR proreceptor to mature IGF-IR and causes short stature and IUGR.

Adolescent↗