Homozygosity mapping and targeted genomic sequencing reveal the gene responsible for cerebellar hypoplasia and quadrupedal locomotion in a consanguineous kindred.

The biological basis for the development of the cerebro-cerebellar structures required for posture and gait in humans is poorly understood. We investigated a large consanguineous family from Turkey exhibiting an extremely rare phenotype associated with quadrupedal locomotion, mental retardation, and cerebro-cerebellar hypoplasia, linked to a 7.1-Mb region of homozygosity on chromosome 17p13.1-13.3. Diffusion weighted imaging and fiber tractography of the patients' brains revealed morphological abnormalities in the cerebellum and corpus callosum, in particular atrophy of superior, middle, and inferior peduncles of the cerebellum. Structural magnetic resonance imaging showed additional morphometric abnormalities in several cortical areas, including the corpus callosum, precentral gyrus, and Brodmann areas BA6, BA44, and BA45. Targeted sequencing of the entire homozygous region in three affected individuals and two obligate carriers uncovered a private missense mutation, WDR81 p.P856L, which cosegregated with the condition in the extended family. The mutation lies in a highly conserved region of WDR81, flanked by an N-terminal BEACH domain and C-terminal WD40 beta-propeller domains. WDR81 is predicted to be a transmembrane protein. It is highly expressed in the cerebellum and corpus callosum, in particular in the Purkinje cell layer of the cerebellum. WDR81 represents the third gene, after VLDLR and CA8, implicated in quadrupedal locomotion in humans.

Surgical treatment of axillary accessory breasts.

Accessory breast tissue is a remnant persisting after normal embryological development of the breast. Although accessory breasts may be asymptomatic, they can cause discomfort during menstruation, anxiety, cosmetic problems, pain, or restriction of arm movement. The data of all patients who presented with axillary accessory breasts between January 2000 and September 2008 were recruited from a computer database. Medical charts, outpatient records, operative notes, and pathology reports were reviewed. A total of 29 patients underwent surgical treatment of axillary accessory breasts in the Department of Breast Surgery and Department of Plastic, Reconstructive and Aesthetic Surgery. The ages of the patients at the time of surgery ranged from 19 to 54 years. The mean age was 28.8 years. All patients were female. Sixteen patients had unilateral accessory breast and 13 patients had bilateral accessory breasts. Fourteen patients had breast hypertrophy. Twenty-one patients had excision, five patients had liposuction, and three patients had both. Axillary accessory breasts can be satisfactorily treated with excision, liposuction, or both. In patients with concomitant macromastia, reduction mammaplasty and removal of accessory breasts can be performed at the same time with no additional morbidity.

Anthropometric measurements in male breast cancer.

BACKGROUND: 1% of breast cancers occur in men. The etiology is obscure. An elevated BMI has been postulated to be a cause. METHODS: All male breast cancer patients operated from January 1990 to May 2001 were retrospectively reviewed. Relation between BMI and male breast cancer was examined. RESULTS: 43 males underwent breast surgery for breast cancer during this period. 3 patients were excluded from the study because of other risk factors for breast cancer. The average BMI of 40 patients was 26.54 kg/m2, which is mildly above the level for normal weight. CONCLUSIONS: Excessive adipose tissue may increase risk of male breast cancer.

Simultaneous excision of ipsilateral nonpalpable multiple breast lesions using radioguided occult lesion localization.

The purpose of this study was to determine the feasibility and effectiveness of ROLL technique for the identification and excision of ipsilateral nonpalpable multiple breast lesions. Between August 2005 and August 2010, eight women, aged 40-61 years, with a radiographic evidence of two separate nonpalpable lesions within the same breast underwent ROLL, as we termed it, double-ROLL. Each lesion was localized with Tc-99m-labeled human serum albumin macroaggregate under ultrasonography or mamography control. A gamma probe was used to guide surgical excisions. There was no radiotracer overlapping or extravasation in any case. Out of the 16 resected specimens, histopathologic examination revealed benign findings in 13 lesions and malignancy in 3. There was no lesion involvement at the surgical margins, and no residuals were detected in any of the benign cases during follow-up. Double-ROLL technique is feasible and safe for the identification and excision of such multiple ipsilateral breast lesions.

CCND1 and CDKN1B polymorphisms and risk of breast cancer.

BACKGROUND AND OBJECTIVES: Previous studies have shown alterations in the cell cycle regulatory proteins in breast carcinomas. However, the results of these studies remain controversial. Cyclin D1 (CCND1) and p27(KIP1) (CDKN1B) are two essential regulators of cell cycle progression. This study aimed to investigate the associations of CCND1 A870G and CDKN1B C79T polymorphisms with breast cancer risk. PATIENTS AND METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotype and allelic frequencies of polymorphisms. Seventy-eight breast cancer patients and 84 age-matched healthy controls were included in the study. RESULTS: Frequencies of CT genotype and T allele of CDKN1B were found to be higher in breast cancer patients than in controls (p=0.013, OR: 1.514 95% CI: 1.086-2.114.15; p=0.007, OR=1.496; 95% CI: 1.111-2.014, respectively). The frequency of AA genotype of CCND1 was decreased in hormone receptor- (estrogen and progesterone receptors) negative patients with breast cancer (p<0.049, OR=0.286; 95% CI: 0.071-1.142) CONCLUSIONS: Even though CDKN1B polymorphism appears to be an important predictive factor for breast cancer risk and CCND1 polymorphism may be a prognostic biomarker for breast cancer, further investigations with larger study groups are needed to fully elucidate the role of CCND1 and CDKN1B polymorphisms in the development and prognosis of breast cancer.

Radioguided occult lesion localization (ROLL) for non-palpable breast cancer: a comparison between day-before and same-day protocols.

BACKGROUND: Although radioguided occult lesion localization (ROLL) has become a widely accepted technique, the optimal time interval between the radioisotope injection and surgery has not yet been determined. AIM: To delineate the effects of time from the injection of the radionuclide until surgery on the ROLL success rate in a patient population diagnosed as having non-palpable breast cancer. METHODS: Between December 2004 and May 2009, 75 patients underwent ROLL procedure. The day-before protocol and same-day protocols included 50 and 25 breast cancer patients respectively. RESULTS: The two study groups were comparable in terms of age, localization technique, radiological findings and the type of surgical procedures (P > 0.05). No statistically significant difference was noticed in the pathological diagnosis, cancer size and the surgical margin clearance between the two groups (P > 0.05). CONCLUSIONS: Same-day injection of the radiotracer was not superior to the day-before injection in ROLL. The day-before protocol can be scheduled for the convenience of both patients and hospital staff.