A NOVEL MUTATION IN NPR2 GENE IN A PATIENT WITH ACROMESOMELIC DYSPLASIA, MAROTEAUX TYPE.

Acromesomelic dysplasia, Maroteaux type (AMDM) is a rare autosomal recessive disease characterized by disproportionate shortening of skeletal elements, predominantly affecting the middle segments (forearms and forelegs) and distal segments (hands and feet) of appendicular skeleton. Furthermore it is related to axial skeleton and leads to wedging of vertebral bodies, with shorter dorsal margins than the ventral margins. Bartels et al. defined mutations in NPR2 gene, encoding natriuretic peptide receptor B (NPR-B), underlying Acromesomelic dysplasia, type Maroteaux. We present here molecular and clinical findings of a case with AMDM. In a patient, a novel homozygous mutation c.1435C>T p.R479X in exon 7 of NPR2 gene was found. Further testing confirmed the heterozygous carrier status of the parents. Our findings expand the spectrum of causative mutations in AMDM.

A novel mutation in the FRAS1 gene in a patient with Fraser syndrome.

Fraser Syndrome (FS) is a rare disease with autosomal recessive inheritance characterized by cryptophthalmus, cutaneous syndactyly, laryngeal and urogenital anomalies. Mutations in the genes FRAS1 and FREM2 encoding components of a protein complex of the extracellular matrix, and recently also mutations in GRIP1 have been found to be causative for FS. We present here molecular and clinical findings of a patient with FS who was found to have a novel homozygous frameshift mutation c.9739delA, p.(T3247Pfs*44) in exon 63 of FRAS1 gene. Further testing confirmed the heterozygous carrier status of parents.

A fertile patient with 45X/47XXX mosaicism.

Turner syndrome (TS) is a sex chromosome abnormality with a frequency of 1/2,000-3,000 among female live births. Characteristic findings are short stature and gonadal dysgenesis. Short and webbed neck, low posterior hairline, broad chest, widespread nipples, cubitus valgus, short 4th and 5th metacarpals, multiple pigmented nevi, primary amenorrhea, lack of secondary sexual characteristics, cardiovascular and renal anomalies are the most common presentations. Most of the cases are infertile. Spontaneous pregnancy is unusual and the risk for congenital anomaly, spontaneous abortion, stillbirth and aneuploidy is increased. Fifty percent of the patients have classical monosomy X (45,X). However mosaicism of 45,X/47,XXX is rare and accounts for 1.7% of the TS cases. Some cases may not reflect the characteristic phenotype. Some cases with normal height, normal menstrual cyclus and fertility have been defined before. The case we present herein is a 26 years old woman who was admitted to our clinic due to recurrent pregnancy loss. In her medical history she had type 1 diabetes mellitus and endometrium cancer, in her family history her mother had recurrent pregnancy loss. The patient's first, third, fourth, fifth and sixth pregnancies had resulted in spontaneous abortions in the first trimester. She had a healthy daughter with 46,XX karyotype from her second pregnancy. A 45,X[8]/47,XXX[12] karyotype was detected by conventional cytogenetic analysis of the patient who did not have dysmorphic findings. The mosaicism was confirmed by FISH analysis with CEP X probe. Of the 100 cells evaluated, 65 of them had 3 signals of X chromosome while 35 had 1 signal. We present the case because of its scarcity in the literature.